ABSTRACT
(1) Background: Anemia affects about 40% of patients with chronic kidney disease (CKD). Daprodustat improves serum hemoglobin in anemic patients by inhibiting prolyl hydroxylase of hypoxia-inducible factor. We conducted a network meta-analysis to investigate the direct and indirect effects of different doses of daprodustat compared to each other and erythropoietin and placebo. (2) Methods: We searched PubMed, Cochrane Library, Web of Science, and Scopus, for randomized clinical trials (RCTs) reporting data about different doses of daprodustat for anemia in nondialysis of CKDs. (3) Results: We eventually included five RCTs with a total sample size of 4566 patients. We found that the higher the dose of daprodustat, the greater the change in serum total iron binding capacity (TIBC), hemoglobin, and ferritin from baseline. Compared to placebo, daprodustat 25-30 mg was associated with the highest significant increase in serum hemoglobin (MD = 3.27, 95% CI = [1.89; 4.65]), a decrease in serum ferritin (MD = -241.77, 95% CI = [-365.45; -118.09]) and increase in serum TIBC (MD = 18.52, 95% CI = [12.17; 24.87]). (4) Conclusion: Higher daprodustat doses were associated with a higher impact on efficacy outcomes as serum total iron-binding capacity (TIBC), hemoglobin, and ferritin. However, data about the safety profile of different doses of daprodustat is still missing.
ABSTRACT
OBJECTIVE: To present the interim findings from a national study investigating the safety and efficacy of convalescent plasma (CP) containing detectable IgG antibodies as a treatment strategy for severe coronavirus disease 2019 (COVID-19). TRIAL DESIGN AND PARTICIPANTS: An open label, two-arm, phase-II clinical trial conducted across 22 hospitals from Saudi Arabia. The intervention group included 40 adults (aged ≥18 years) with confirmed severe COVID-19 and the control group included 124 patients matched using propensity score for age, gender, intubation status, and history of diabetes and/or hypertension. Intervention group included those (a) with severe symptoms (dyspnea; respiratory rate, ≥30/min; SpO2, ≤93%, PaO2/FiO2 ratio, <300; and/or lung infiltrates >50% within 24-48 h), (b) requiring intensive care unit (ICU) care or (c) experiencing life-threatening conditions. The control group included confirmed severe COVID-19 patients of similar characteristics who did not consent for CP infusion or were not able to receive CP due to its nonavailability. INTERVENTIONS: The intervention group participants were infused 300 ml (200-400 ml/treatment dose) CP at least once, and if required, daily for up to 5 sessions, along with receiving the best standard of care. The control group only received the best standard of care. OUTCOMES: The primary endpoints were safety and ICU length of stay (LOS). The secondary endpoints included 30-day mortality, days on mechanical ventilation and days to clinical recovery. RESULTS: CP transfusion did not result in any adverse effects. There was no difference in the ICU LOS (median 8 days in both groups). The mortality risk was lower in the CP group: 13% absolute risk reduction (P = 0.147), hazard ratio (95% confidence interval): 0.554 (0.299-1.027; P = 0.061) by log-rank test. There was no significant difference in the days on mechanical ventilation and days to clinical recovery. CONCLUSION: CP containing detectable antibodies is a safe strategy and may result in a decrease in mortality in patients with severe COVID-19. The results of the completed trial with a larger study sample would provide more clarity if this difference in mortality is significant. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04347681; Saudi Clinical Trials Registry No.: 20041102.
ABSTRACT
Fasting Ramadan is known to influence patients' medication adherence. Data on patients' behavior to oral anticoagulant (OAC) drug intake during Ramadan is missing. We aimed to determine patient-guided modifications of OAC medication regimen during Ramadan and to evaluate its consequences. A multicenter cross-sectional study conducted in Saudi Arabia. Data were collected shortly after Ramadan 2019. Participants were patients who fasted Ramadan and who were on long-term anticoagulation. Patient-guided medication changes during Ramadan in comparison to the regular intake schedule before Ramadan were recorded. Modification behavior was compared between twice daily (BID) and once daily (QD) treatment regimens. Rates of hospital admission during Ramadan were determined. We included 808 patients. During Ramadan, 53.1% modified their intake schedule (31.1% adjusted intake time, 13.2% skipped intakes, 2.2% took double dosing). A higher frequency of patient-guided modification was observed in patients on BID regimen compared to QD regimen. During Ramadan, 11.3% of patients were admitted to hospital. Patient-guided modification was a strong predictor for hospital admission. Patient-guided modification of OAC intake during Ramadan is common, particularly in patients on BID regimen. It increases the risk of hospital admission during Ramadan. Planning of OAC intake during Ramadan and patient education on the risk of low adherence are advisable.
