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1.
Kidney Int Rep ; 2022 Aug 04.
Article in English | MEDLINE | ID: covidwho-1966542

ABSTRACT

Introduction: Home over center-based dialysis may minimize SARS-CoV2 exposure risks. We explored how the pandemic may have introduced challenges related to peritoneal dialysis (PD) supply availability, routine patient care, and how facility practices changed during this time. Methods: The Peritoneal Dialysis/Dialysis Outcomes and Practice Patterns Study (PDOPPS/DOPPS) and International Society of Nephrology (ISN) administered a web-based survey (November 2020 - March 2021). Medical director responses were compared across 10 ISN regions. Results: 165 PD facilities (51 countries) returned surveys. During the initial COVID-19 wave, the reported frequency of in-person patient visits decreased in 9 of 10 ISN regions. Before the pandemic, most facilities required a mask during PD exchanges which continued over the course of the pandemic. Although most facilities in different regions did not report PD supply disruptions, sites in Africa and South Asia reported major disruptions. Reductions in laparoscopic surgical procedures for PD catheters were reported by facilities in 9 out of 10 regions while non-surgical percutaneous procedures increased in facilities in 6 regions. Training of new PD patients declined in facilities in each region. Increased use of remote technology by patients to communicate with clinics was observed in all regions compared to pre-pandemic levels. Conclusion: Marked within- and across-region variability was noted in PD facility burden, clinical practice, and adaptation to the COVID-19 pandemic. This study highlights opportunities to improve routine PD care, adapt to the ongoing pandemic, and increase preparedness for potential future interruptions in PD care.

2.
Kidney Diseases ; : 1-11, 2022.
Article in English | Web of Science | ID: covidwho-1909939

ABSTRACT

Background: The COVID-19 pandemic is challenging healthcare systems worldwide and has placed hospitals and healthcare providers (HCPs) at the center of a global crisis. Disruptions to hospital priorities, and limitations placed on the mobility of societies, have contributed to changes in the way HCPs and patients view and access dialysis for kidney failure, including which dialysis modality is preferred. Summary: This article explores the dialysis experience within the COVID-19 pandemic environment in the Asia Pacific region and presents evidence that peritoneal dialysis (PD) provides benefits to patients, HCPs, and health systems. As the number of people infected with COVID-19 has increased, the advantages of PD as a dialysis modality for limiting the spread of COVID-19 infection has been recognized. Key Message: The utility of PD has been demonstrated during the COVID-19 pandemic;thus, ensuring that the usage of PD is maintained and increased in a post-pandemic future is key. Such a scenario could enhance our ability to care for patients without interruption in circumstances of unforeseen obstacles and supports the ability of healthcare systems and patients to overcome barriers to dialysis access.

3.
BMJ Open ; 12(6): e059540, 2022 06 01.
Article in English | MEDLINE | ID: covidwho-1874561

ABSTRACT

OBJECTIVES: To determine whether hydroxychloroquine when used with personal protective equipment reduces the proportion of laboratory-confirmed COVID-19 among healthcare workers in comparison to the use of personal protective equipment alone. DESIGN: Multicentre, parallel-group, open-label randomised trial. Enrolment started on 29 June 2020 and stopped on 4 February 2021. Participants randomised in HydrOxychloroquine Prophylaxis Evaluation were followed for 6 months. SETTING: 9 hospitals across India. PARTICIPANTS: Healthcare workers in an environment with exposure to COVID-19 were randomised in a 1:1 ratio to hydroxychloroquine plus use of personal protective equipment or personal protective equipment alone. 886 participants were screened and 416 randomised (213 hydroxychloroquine arm and 203 personal protective equipment). INTERVENTION: Participants in intervention arm received 800 mg of hydroxychloroquine on day of randomisation and then 400 mg once a week for 12 weeks in addition to the use of personal protective equipment. In the control arm, participants continued to use personal protective equipment alone. MAIN OUTCOME: Proportion of laboratory-confirmed COVID-19 in the 6 months after randomisation. RESULTS: Participants were young (mean age 32.1 years, SD 9.1 years) with low-comorbid burden. 47.4% were female. In the 6 months after randomisation (primary analysis population=413), 11 participants assigned to the hydroxychloroquine group and 12 participants assigned to the standard practice group met the primary endpoint (5.2% vs 5.9%; OR 0.85, 95% CI 0.35 to 2.07, p=0.72). There was no heterogeneity of treatment effect in any prespecified subgroup. There were no significant differences in the secondary outcomes. The adverse event rates were 9.9% and 6.9% in the hydroxychloroquine and standard practice arms, respectively. There were no serious adverse events in either group. CONCLUSIONS AND RELEVANCE: Hydroxychloroquine along with personal protective equipment was not superior to personal protective equipment alone on the proportion of laboratory-confirmed COVID-19. Definitive conclusions are precluded as the trial stopped early for futility, and hence was underpowered. TRIAL REGISTRATION NUMBER: CTRI/2020/05/025067.


Subject(s)
COVID-19 , Personal Protective Equipment , Adult , COVID-19/drug therapy , COVID-19/prevention & control , Female , Health Personnel , Humans , Hydroxychloroquine/therapeutic use , India/epidemiology , Male
4.
Clin Kidney J ; 15(7): 1312-1321, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1868268

ABSTRACT

Background: To investigate the anti-spike antibody response to vaccination in kidney transplant recipients (KTRs) previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as compared with KTRs with no history of coronavirus disease 2019 (COVID-19) from India. Methods: SARS-CoV-2 spike immunoglobulin (Ig) G antibody response was measured in 105 post-COVID-19 KTRs with PCR-confirmed SARS-CoV-2 infection who received either no vaccination (cohort 1), a single dose (cohort 2) or two doses (cohort 3) of vaccine and compared with 103 two-dose vaccinated COVID-19-naïve KTRs with no history of COVID-19 (cohort 4). Results: Out of 103 COVID-19-naïve two-dose vaccinated KTRs, <50% became seropositive with anti-spike antibody titres >50 arbitrary unit/mL subsequent to complete vaccination, the seroconversion rate being comparable in subjects receiving CovishieldTM versus CovaxinTM vaccines. However, the seropositive KTRs vaccinated with CovishieldTM had higher anti-spike antibody titres as compared with those who received CovaxinTM. We observed higher anti-SARS-CoV-2 spike antibody levels in post-COVID-19 KTRs after one dose of vaccine as compared with COVID-19-naïve two-dose vaccinated KTRs. Importantly, the second dose in post-COVID-19 KTRs did not significantly increase anti-spike antibody levels compared with the single-dose recipients. Conclusions: Our data present that in KTRs with previous SARS-CoV-2 infection, a single dose of vaccine (CovishieldTM) may be effective in mounting an optimal immune response. In contrast, COVID-19-naïve two-dose vaccinated KTRs respond poorly (<50%) to the current recommendation of a two-dose regimen in India.

5.
Trials ; 22(1): 573, 2021 Aug 28.
Article in English | MEDLINE | ID: covidwho-1817236

ABSTRACT

BACKGROUND: SARS-CoV-2 binds to membrane-bound angiotensin-converting enzyme 2 (ACE2) which may result in downregulation of membrane-bound ACE2. ACE2 is a key regulator of the renin-angiotensin system (RAS) and is responsible for degrading angiotensin II and thereby counteracting its pro-inflammatory, pro-fibrotic effects mediated through the angiotensin II type 1 receptor (AT1R). As AT1R is directly blocked by angiotensin receptor blockers (ARBs), these agents may offer a safe, low-cost solution for reducing COVID-19 respiratory outcomes. METHODS AND DISCUSSION: CLARITY is a pragmatic, adaptive, two-arm, multi-centre, comparative effectiveness phase III randomised controlled trial that examines whether ARBs reduce COVID-19 severity among high-risk patients. Recruiting in India and Australia, the trial will compare treatment with a maximum tolerated daily dose of an ARB to standard of care. Treatment allocation is blinded in India but open-label in Australia due to interruptions to placebo supply in the latter. The primary endpoint is a 7-point ordinal scale of clinical states, ranging from no limitation of activities (category 1) to death (category 7), assessed on day 14. Secondary outcomes include the 7-point scale assessed at day 28 and 28- and 90-day mortality. The design adapts the sample size based on accumulating data via frequent interim analyses and the use of predictive probability to determine whether the current sample size is sufficient or continuing accrual would be futile. The trial commenced recruitment on 18 August 2020. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04394117 . Registered on 19 May 2020. Clinical Trial Registry of India: CTRI/2020/07/026831).


Subject(s)
Angiotensin Receptor Antagonists , COVID-19 , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Renin-Angiotensin System , SARS-CoV-2
6.
Nephrology (Carlton) ; 27(5): 391-403, 2022 May.
Article in English | MEDLINE | ID: covidwho-1799261

ABSTRACT

Peritoneal dialysis (PD) has several advantages compared to haemodialysis (HD), but there is evidence showing underutilization globally, especially in low-income and lower-middle-income countries (LLMICs) where kidney replacement therapies (KRT) are often unavailable, inaccessible, and unaffordable. Only 11% of all dialysis patients worldwide use PD, more than 50% of whom live in China, the United States of America, Mexico, or Thailand. Various barriers to increased PD utilization have been reported worldwide including patient preference, low levels of education, and lower provider reimbursement. However, unique but surmountable barriers are applicable to LLMICs including the excessively high cost of providing PD (related to PD fluids in particular), excessive cost of treatment borne by patients (relative to HD), lack of adequate PD training opportunities for doctors and nurses, low workforce availability for kidney care, and challenges related to some PD outcomes (catheter-related infections, hospitalizations, mortality, etc.). This review discusses some known barriers to PD use in LLMICs and leverages data that show a global trend in reducing rates of PD-related infections, reducing rates of modality switches from HD, and improving patient survival in PD to discuss how PD use can be increased in LLMICs. We therefore, challenge the idea that low PD use in LLMICs is unavoidable due to these barriers and instead present opportunities to improve PD utilization in LLMICs.


Subject(s)
Kidney Failure, Chronic , Peritoneal Dialysis , Developing Countries , Dialysis Solutions , Humans , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Peritoneal Dialysis/adverse effects , Renal Dialysis , United States
7.
Intensive Care Med ; 48(5): 580-589, 2022 05.
Article in English | MEDLINE | ID: covidwho-1797659

ABSTRACT

PURPOSE: We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. METHODS: We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. RESULTS: We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference - 4.3%; 99% confidence interval (CI) - 11.7-3.0; relative risk 0.89; 0.72-1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI - 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (- 3 to 10; P = 0.22). CONCLUSION: Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.


Subject(s)
COVID-19 , Dexamethasone , Hypoxia , Adult , COVID-19/complications , COVID-19/drug therapy , Dexamethasone/administration & dosage , Dose-Response Relationship, Drug , Humans , Hypoxia/complications , Hypoxia/drug therapy , Patient Acuity , Quality of Life , Surveys and Questionnaires , Treatment Outcome
8.
BMJ : British Medical Journal (Online) ; 377, 2022.
Article in English | ProQuest Central | ID: covidwho-1784790

ABSTRACT

Tracking national legal frameworks to accelerate action on health for all

9.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329890

ABSTRACT

Background: SARS-CoV-2 infection is associated with a significant risk of hospitalisation, death, and prolonged impact on quality of life. Evaluation of new treatment options and optimising therapeutic management of people hospitalised with SARS-CoV-2 infection remains essential, but rapid changes in pandemic conditions and potential therapies have limited the utility of traditional approaches to randomised controlled trials. Methods ASCOT ADAPT is an international, investigator-initiated, adaptive platform, randomised controlled trial of therapeutics for non-critically ill patients hospitalised with COVID-19. The study design is open label and pragmatic. Potential participants are hospitalised adults with PCR confirmed, symptomatic, SARS-CoV-2 infection, within 14 days of symptom onset. Domains include antiviral, antibody and anticoagulant interventions, with a composite primary outcome of 28-day mortality or progression to intensive-care level respiratory or haemodynamic support. Initial interventions include intravenous nafamostat and variable dose anticoagulation. A range of secondary endpoints, and substudies for specific domains and interventions are outlined. Discussion This paper presents the trial protocol and management structure, including international governance, remote site monitoring and biobanking activities, and provides commentary on ethical and pragmatic considerations in establishing the ASCOT ADAPT trial under pandemic conditions.

10.
Clinical kidney journal ; 2022.
Article in English | EuropePMC | ID: covidwho-1733205

ABSTRACT

Background To investigate the anti-spike antibody response to vaccination in Kidney transplant recipients (KTRs) previously infected with SARS-CoV-2 as compared to KTRs with no history of COVID-19 from India. Methods SARS-CoV-2 spike immunoglobulin (Ig) G antibody response was measured in 105 post COVID-19 KTRs with PCR confirmed SARS-CoV-2 infection who received either no vaccination (cohort 1), single (cohort 2) or two doses (cohort 3) of vaccine and compared to 103 two-dose vaccinated COVID-19 naïve KTRs with no history of COVID-19 (cohort 4). Results Out of 103 COVID-19 naïve two-dose vaccinated KTRs, less than 50% became seropositive with anti-spike antibody titres > 50AU/mL subsequent to complete vaccination, the seroconversion rate being comparable in subjects receiving CovishieldTM versus CovaxinTM vaccines. However, the seropositive KTRs vaccinated with CovishieldTM had higher anti-spike antibody titres as compared to those who received CovaxinTM. We observed higher anti-SARS-CoV-2 spike antibody levels in post COVID-19 KTRs after 1 dose of vaccine as compared with COVID-19 naïve two-dose vaccinated KTRs. Importantly, the second dose in post COVID-19 KTRs did not significantly increase anti-spike antibody levels compared with the single dose recipients. Conclusions Our data presents that in KTRs with previous SARS-CoV-2 infection a single dose of vaccine (CovishieldTM) may be effective in mounting optimal immune response. In contrast, COVID-19 naïve two-dose vaccinated KTRs respond poorly (<50%) to current recommendation of a two-dose regimen in India.

11.
Kidney Int Rep ; 7(5): 971-982, 2022 May.
Article in English | MEDLINE | ID: covidwho-1734374

ABSTRACT

Introduction: It is unknown how the COVID-19 pandemic has affected the care of vulnerable chronic hemodialysis (HD) patients across regions, particularly in low and lower-middle income countries (LLMICs). We aimed to identify global inequities in HD care delivery during the COVID-19 pandemic. Methods: The ISN and the Dialysis Outcomes and Practice Patterns Study (DOPPS) conducted a global online survey of HD units between March and November, 2020, to ascertain practice patterns and access to resources relevant to HD care during the COVID-19 pandemic. Responses were categorized according to World Bank income classification for comparisons. Results: Surveys were returned from 412 facilities in 78 countries: 15 (4%) in low-income countries (LICs), 111 (27%) in lower-middle income countries (LMICs), 145 (35%) in upper-middle income countries (UMICs), and 141 (34%) in high-income countries (HICs). Respondents reported that diagnostic tests for SARS-CoV-2 were unavailable or of limited availability in LICs (72%) and LMICs (68%) as compared with UMICs (33%) and HICs (20%). The number of patients who missed HD treatments was reported to have increased during the COVID-19 pandemic in LICs (64%) and LMICs (67%) as compared with UMICs (31%) and HICs (6%). Limited access to HD, intensive care unit (ICU) care, and mechanical ventilation among hospitalized patients on chronic dialysis with COVID-19 were also reportedly higher in LICs and LMICs as compared with UMICs and HICs. Staff in LLMICs reported less routine testing for SARS-CoV-2 when asymptomatic as compared with UMICs and HICs-14% in LICs and 11% in LMICs, compared with 26% and 28% in UMICs and HICs, respectively. Severe shortages of personal protective equipment (PPE) were reported by the respondents from LICs and LMICs compared with UMICs and HICs, especially with respect to the use of the N95 particulate-air respirator masks. Conclusion: Striking global inequities were identified in the care of chronic HD patients during the pandemic. Urgent action is required to address these inequities which disproportionately affect LLMIC settings thereby exacerbating pre-existing vulnerabilities that may contribute to poorer outcomes.

12.
Kidney Int Rep ; 7(3): 397-409, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1649355

ABSTRACT

INTRODUCTION: To assess the impact of the COVID-19 pandemic impact on hemodialysis (HD) centers, The Dialysis Outcomes and Practice Patterns Study and ISN collaborated on a web-survey of centers. METHODS: A combined approach of random sampling and open invitation was used between March 2020 and March 2021. Responses were obtained from 412 centers in 78 countries and all 10 ISN regions. RESULTS: In 8 regions, rates of SARS-CoV-2 infection were <20% in most centers, but in North East Asia (NE Asia) and Newly Independent States and Russia (NIS & Russia), rates were ≥20% and ≥30%, respectively. Mortality was ≥10% in most centers in 8 regions, although lower in North America and Caribbean (N America & Caribbean) and NE Asia. Diagnostic testing was not available in 33%, 37%, and 61% of centers in Latin America, Africa, and East and Central Europe, respectively. Surgical masks were widely available, but severe shortages of particulate-air filter masks were reported in Latin America (18%) and Africa (30%). Rates of infection in staff ranged from 0% in 90% of centers in NE Asia to ≥50% in 63% of centers in the Middle East and 68% of centers in NIS & Russia. In most centers, <10% of staff died, but in Africa and South Asia (S Asia), 2% and 6% of centers reported ≥50% mortality, respectively. CONCLUSION: There has been wide global variation in SARS-CoV-2 infection rates among HD patients and staff, personal protective equipment (PPE) availability, and testing, and the ways in which services have been redesigned in response to the pandemic.

13.
Intensive Care Med ; 48(1): 45-55, 2022 01.
Article in English | MEDLINE | ID: covidwho-1605102

ABSTRACT

PURPOSE: We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. METHODS: We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. RESULTS: The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. CONCLUSION: We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.


Subject(s)
COVID-19 , Bayes Theorem , COVID-19/drug therapy , Dexamethasone , Humans , Hypoxia , SARS-CoV-2 , Steroids
15.
N Engl J Med ; 385(25): 2325-2335, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1575626

ABSTRACT

BACKGROUND: Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (PHIs) are as effective as erythropoiesis-stimulating agents (ESAs) in increasing hemoglobin levels. METHODS: In this randomized, open-label, phase 3 trial, we assigned patients with CKD who were undergoing dialysis and who had a hemoglobin level of 8.0 to 11.5 g per deciliter to receive an oral HIF-PHI (daprodustat) or an injectable ESA (epoetin alfa if they were receiving hemodialysis or darbepoetin alfa if they were receiving peritoneal dialysis). The two primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 (noninferiority margin, -0.75 g per deciliter) and the first occurrence of a major adverse cardiovascular event (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), with a noninferiority margin of 1.25. RESULTS: A total of 2964 patients underwent randomization. The mean (±SD) baseline hemoglobin level was 10.4±1.0 g per deciliter overall. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.28±0.02 g per deciliter in the daprodustat group and 0.10±0.02 g per deciliter in the ESA group (difference, 0.18 g per deciliter; 95% confidence interval [CI], 0.12 to 0.24), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 2.5 years, a major adverse cardiovascular event occurred in 374 of 1487 patients (25.2%) in the daprodustat group and in 394 of 1477 (26.7%) in the ESA group (hazard ratio, 0.93; 95% CI, 0.81 to 1.07), which also met the prespecified noninferiority margin for daprodustat. The percentages of patients with other adverse events were similar in the two groups. CONCLUSIONS: Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-D ClinicalTrials.gov number, NCT02879305.).


Subject(s)
Anemia/drug therapy , Barbiturates/therapeutic use , Darbepoetin alfa/therapeutic use , Epoetin Alfa/therapeutic use , Glycine/analogs & derivatives , Hematinics/therapeutic use , Renal Dialysis , Renal Insufficiency, Chronic/complications , Aged , Anemia/etiology , Barbiturates/adverse effects , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Darbepoetin alfa/adverse effects , Epoetin Alfa/adverse effects , Female , Glycine/adverse effects , Glycine/therapeutic use , Hematinics/adverse effects , Hemoglobins/analysis , Humans , Hypoxia-Inducible Factor-Proline Dioxygenases/antagonists & inhibitors , Intention to Treat Analysis , Male , Middle Aged , Myocardial Infarction/epidemiology , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/therapy , Stroke/epidemiology
16.
N Engl J Med ; 385(25): 2313-2324, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1575625

ABSTRACT

BACKGROUND: Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. In patients with chronic kidney disease (CKD) who are not undergoing dialysis, the efficacy and safety of daprodustat, as compared with the conventional erythropoiesis-stimulating agent darbepoetin alfa, are unknown. METHODS: In this randomized, open-label, phase 3 trial with blinded adjudication of cardiovascular outcomes, we compared daprodustat with darbepoetin alfa for the treatment of anemia in patients with CKD who were not undergoing dialysis. The primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 and the first occurrence of a major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke). RESULTS: Overall, 3872 patients were randomly assigned to receive daprodustat or darbepoetin alfa. The mean (±SD) baseline hemoglobin levels were similar in the two groups. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.74±0.02 g per deciliter in the daprodustat group and 0.66±0.02 g per deciliter in the darbepoetin alfa group (difference, 0.08 g per deciliter; 95% confidence interval [CI], 0.03 to 0.13), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 1.9 years, a first MACE occurred in 378 of 1937 patients (19.5%) in the daprodustat group and in 371 of 1935 patients (19.2%) in the darbepoetin alfa group (hazard ratio, 1.03; 95% CI, 0.89 to 1.19), which met the prespecified noninferiority margin of 1.25. The percentages of patients with adverse events were similar in the two groups. CONCLUSIONS: Among patients with CKD and anemia who were not undergoing dialysis, daprodustat was noninferior to darbepoetin alfa with respect to the change in the hemoglobin level from baseline and with respect to cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-ND ClinicalTrials.gov number, NCT02876835.).


Subject(s)
Anemia/drug therapy , Barbiturates/therapeutic use , Darbepoetin alfa/therapeutic use , Glycine/analogs & derivatives , Hematinics/therapeutic use , Renal Insufficiency, Chronic/complications , Aged , Anemia/etiology , Barbiturates/adverse effects , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Darbepoetin alfa/adverse effects , Female , Glycine/adverse effects , Glycine/therapeutic use , Hematinics/adverse effects , Hemoglobins/analysis , Humans , Hypoxia-Inducible Factor-Proline Dioxygenases/antagonists & inhibitors , Intention to Treat Analysis , Male , Middle Aged , Myocardial Infarction/epidemiology , Renal Insufficiency, Chronic/blood , Stroke/epidemiology
17.
Lancet Infect Dis ; 21(11): e342-e347, 2021 11.
Article in English | MEDLINE | ID: covidwho-1561809

ABSTRACT

Large-scale deployment of COVID-19 vaccines will seriously affect the ongoing phases 2 and 3 randomised placebo-controlled trials assessing SARS-CoV-2 vaccine candidates. The effect will be particularly acute in high-income countries where the entire adult or older population could be vaccinated by late 2021. Regrettably, only a small proportion of the population in many low-income and middle-income countries will have access to available vaccines. Sponsors of COVID-19 vaccine candidates currently in phase 2 or initiating phase 3 trials in 2021 should consider continuing the research in countries with limited affordability and availability of COVID-19 vaccines. Several ethical principles must be implemented to ensure the equitable, non-exploitative, and respectful conduct of trials in resource-poor settings. Once sufficient knowledge on the immunogenicity response to COVID-19 vaccines is acquired, non-inferiority immunogenicity trials-comparing the immune response of a vaccine candidate to that of an authorised vaccine-would probably be the most common trial design. Until then, placebo-controlled, double-blind, crossover trials will continue to play a role in the development of new vaccine candidates. WHO or the Council for International Organizations of Medical Sciences should define an ethical framework for the requirements and benefits for trial participants and host communities in resource-poor settings that should require commitment from all vaccine candidate sponsors from high-income countries.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Clinical Trials as Topic , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Double-Blind Method , Humans , Immunogenicity, Vaccine , Pandemics/prevention & control , SARS-CoV-2/immunology
18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296233

ABSTRACT

Background: Healthcare workers (HCWs),particularly from lower-middle income countries (LMIC), are at high risk of acquiring COVID-19. Limited data exist on the effectiveness of hydroxychloroquine as prophylaxis. Our trial evaluated the effectiveness of a 12-week regimen of hydroxychloroquine among HCWs on the risk of laboratory-confirmed COVID-19 in the 6 months after randomization Methods: We conducted a multicentre parallel-group open-label randomized controlled trial in 9 centres across India. HCWs serving in an environment with exposure to COVID-19 were eligible and randomized in a 1:1 ratio to hydroxychloroquine plus standard practice or to standard practice alone (role-appropriate personal protective equipment). In the intervention arm, participants received 2 doses of 400mg hydroxychloroquine at randomization followed by a weekly dose for 12 weeks. The primary outcome was the proportion of laboratory-confirmed COVID-19 in the 6 months after randomization using an intention-to-treat analysis. The trial was registered on Clinical Trials Registry of India(CTRI/2020/05/025067). Findings: From 29th June 2020 to 4th February 2021, 886 participants were screened and 416 were randomized (203-standard practice and 213- hydroxychloroquine plus standard practice). In the 6 months after randomization (primary analysis population=413), 11 participants assigned to the hydroxychloroquine group and 12 participants assigned to the standard practice group met the primary end point[ 5.1% vs 5.9%;OR 0.85, [95% CI 0.35-2.06] p=0.71]. There was no heterogeneity of treatment effect on the primary outcome in any of the pre-specified subgroups. There were no significant differences in any of the secondary outcomes. The adverse event rates were 9.9% and 6.9% in the hydroxychloroquine and standard practice arms respectively. There were no serious adverse events in either group. Interpretation: Hydroxychloroquine along with standard practice was not superior to standard practice alone on the proportion of lab-confirmed COVID-19. However, conclusions are limited by the premature trial cessation.Trial Registration: Clinical Trials Registry of India (CTRI/2020/05/025067).Funding: Wesley Medical Research, AustraliaDeclaration of Interest: OJ reports being a member of the WHO R&D Blueprint Safety Monitoring Team, ACT Acclerator-R&D Digital Health working group and COVID-19 Clinical Research Coalition data sharing working group. Remaining authors have nothing to declare. Ethical Approval: Written informed consent was obtained from all participants. Thetrial was approved by the Ethics Committee at all participating sites (coordinating centre EC approval number: The George Institute Ethics Committee:08-2020)

19.
Glob Heart ; 16(1): 66, 2021.
Article in English | MEDLINE | ID: covidwho-1497690

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) has had a continuous and robust impact on world health. The resulting COVID-19 pandemic has had a devastating physical, mental and fiscal impact on the millions of people living with noncommunicable diseases (NCDs). In addition to older age, people living with CVD, stroke, obesity, diabetes, kidney disease, and hypertension are at a particularly greater risk for severe forms of COVID-19 and its consequences. Meta-analysis indicates that hypertension, diabetes, chronic kidney disease, and thrombotic complications have been observed as both the most prevalent and most dangerous co-morbidities in COVID-19 patients. And despite the nearly incalculable physical, mental, emotional, and economic toll of this pandemic, forthcoming public health figures continue to place cardiovascular disease as the number one cause of death across the globe in the year 2020. The world simply cannot wait for the next pandemic to invest in NCDs. Social determinants of health cannot be addressed only through the healthcare system, but a more holistic multisectoral approach with at its basis the Sustainable Development Goals (SDGs) is needed to truly address social and economic inequalities and build more resilient systems. Yet there is reason for hope: the 2019 UN Political Declaration on UHC provides a strong framework for building more resilient health systems, with explicit calls for investment in NCDs and references to fiscal policies that put such investment firmly within reach. By further cementing the importance of addressing circulatory health in a future Framework Convention on Emergency Preparedness, WHO Member States can take concrete steps towards a pandemic-free future. As the chief representatives of the global circulatory health community and patients, the Global Coalition for Circulatory Health calls for increased support for the healthcare workforce, global vaccine equity, embracing new models of care and digital health solutions, as well as fiscal policies on unhealthy commodities to support these investments.


Subject(s)
COVID-19 , Noncommunicable Diseases , Aged , Global Health , Humans , Noncommunicable Diseases/epidemiology , Noncommunicable Diseases/prevention & control , Pandemics/prevention & control , SARS-CoV-2
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