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1.
J Clin Med ; 11(14)2022 Jul 20.
Article in English | MEDLINE | ID: covidwho-1938868

ABSTRACT

Coronavirus disease 2019 (COVID-19) survivors can have lasting signs and symptoms, including various organ damage, indicating that COVID-19 can be a chronic illness. The current study aims to compare the 30-day hospital readmission and death rate of patients admitted to the hospital with COVID-19 and pneumonia due to other causes. A retrospective cohort study was conducted using data from the Saudi National Guard Health Affairs (NGHA). Records of patients admitted with COVID-19 between 1 March 202 and 31 December 2020 (n = 3597) and pneumonia during 2017 and 2019 (n = 6324) were retrieved and analyzed. We compared the likelihood of 30-day hospital readmission, intensive care unit (ICU) admission, and death between the two groups. Compared with the control group, COVID-19 patients had higher odds of 30-day readmission (odds ratio 1.90, 95% confidence interval 1.61-2.24), higher risk of ICU transfer (hazard ratio 1.85, 95% confidence interval 1.65-2.07), more extended hospital stay (7 vs. 4 days), but less risk of death (hazard ratio 0.18, 95% confidence interval 0.14-0.24). The findings that hospital readmission was higher in COVID-19 recovered patients than in other pneumonia patients inform the current discussion about readmission and death in COVID-19 patients.

2.
Lancet Microbe ; 3(1): e11-e20, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1915215

ABSTRACT

BACKGROUND: ChAdOx1-vectored vaccine candidates against several pathogens have been developed and tested in clinical trials and ChAdOx1 nCoV-19 has now been licensed for emergency use for COVID-19. We assessed the safety and immunogenicity of the ChAdOx1 MERS vaccine in a phase 1b trial in healthy Middle Eastern adults. METHOD: MERS002 is an open-label, non-randomised, dose-escalation, phase 1b trial. Healthy Middle Eastern adults aged 18-50 years were included in the study. ChAdOx1 MERS was administered as a single intramuscular injection into the deltoid muscle of the non-dominant arm at three different dose groups: 5·0 × 109 viral particles in a low-dose group, 2·5 × 1010 viral particles in an intermediate-dose group, and 5·0 × 1010 viral particles in a high-dose group. The primary objective was to assess the safety and tolerability of ChAdOx1 MERS, measured by the occurrence of solicited and unsolicited adverse events after vaccination for up to 28 days and occurrence of serious adverse events up to 6 months. The study is registered with ClinicalTrials.gov, NCT04170829. FINDINGS: Between Dec 17, 2019, and June 1, 2020, 24 participants were enrolled (six to the low-dose, nine to the intermediate-dose, and nine to the high-dose group) and received a dose; 23 were available for follow-up at 6 months. The one dose of ChAdOx1 MERS vaccine was well tolerated with no serious adverse event reported during the 6 months of follow-up. Most adverse events were mild (67, 74%) and moderate (17, 19%). Six (7%) severe adverse events were reported by two participants in the intermediate-dose group (two feverish, two headache, one joint pain, and one muscle pain). Pain at the injection site was the most common local and overall adverse event, reported by 15 (63%) of the 24 participants. The most common systemic adverse event was headache, reported by 14 (58%), followed by muscle pain reported by 13 (54%). The vaccine induced both antibody and T cell immune responses in all volunteers; antibodies peaked at day 28 and T cell responses peaked at day 14; and continued until the end of follow-up at 6 months. INTERPRETATION: The acceptable safety and immunogenicity data from this phase 1b trial of ChAdOx1 MERS vaccine candidate in Healthy Middle Eastern adults, combined with previous safety and immunogenicity data from a trial in the UK, support selecting the ChAdOx1 MERS vaccine for advancement into phase 2 clinical evaluation. FUNDING: UK Department of Health and Social Care, using UK Aid funding, managed by the UK National Institute for Health Research; and King Abdullah International Medical Research Center.


Subject(s)
COVID-19 , Adult , Antibodies, Viral , COVID-19/prevention & control , Coronavirus Infections/prevention & control , Headache , Humans , Immunogenicity, Vaccine , Myalgia , Vaccines, DNA , Viral Vaccines
3.
Cureus ; 14(5), 2022.
Article in English | EuropePMC | ID: covidwho-1887551

ABSTRACT

Background: Kidney transplant recipients appear to be at high risk for critical coronavirus disease 2019 (COVID-19) illness. They are considered a priority for COVID-19 vaccination. Only a few studies report on the safety and efficacy of the COVID-19 vaccine in these patients. Methods: In this prospective observational study, we measured anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) spike-specific IgG post first and second COVID-19 mRNA vaccines in 113 kidney transplant recipients and compared them to 62 healthy volunteers. Result: After the first COVID-19 vaccine, SARS-CoV-2-specific antibodies were undetectable in 38.9% of kidney transplant recipients, and after the second, it remained undetectable in 12.4%. SARS-CoV-2-specific antibodies were significantly lower in kidney transplant recipients. The average antibody titer after the first vaccine was 1243.6±4137.5 in kidney transplant recipients compared to 20012.2±44436.4 in the controls after the first dose (P=0.002), and 7965.5±12431.3 versus 82891.3±67418.7, respectively, after the second dose (P <0.001). The immune response to the COVID-19 vaccine seemed to be influenced by mycophenolate dose in kidney transplant recipients and pre-vaccination infection. Conclusion: Kidney transplant recipients are prone to have attenuated antibody responses (anti-spike IgGs) to mRNA COVID-19 vaccines. Patients on mycophenolate mofetil (2 gm daily) had significantly lower SARS-CoV-2 spike-specific IgG levels as compared to patients on no or reduced dose of mycophenolate. Hence, kidney transplant recipients need to continue all infection control precautionary measures against COVID-19 infection and should be considered a priority for a third COVID-19 vaccine.

4.
Ann Thorac Med ; 17(2): 81-86, 2022.
Article in English | MEDLINE | ID: covidwho-1810636

ABSTRACT

INTRODUCTION: There are limited direct data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) long-term immune responses and reinfection. This study aimed to evaluate the rate, risk factors, and severity of COVID-19 reinfection. METHODS: This retrospective cohort study included five hospitals across Saudi Arabia. All subjects who were presented or admitted with positive SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) tests were evaluated between March 2020 and August 2021. Reinfection was defined as a patient who was infected followed by clinical recovery, and later became infected again 90 days post first infection. The infection was confirmed with a positive SARS-CoV-2 (RT-PCR). Four hundred and seventeen recovered cases but with no reinfection were included as a control. RESULTS: A total of 35,288 RT-PCR-confirmed COVID-19 patients were observed between March 2020 and August 2021. Based on the case definition, (0.37%) 132 patients had COVID-19 reinfection. The mean age in the reinfected cases was 40.95 ± 19.48 (range 1-87 years); Females were 50.76%. Body mass index was 27.65 ± 6.65 kg/m2; diabetes and hypertension were the most common comorbidities. The first infection showed mild symptoms in 91 (68.94%) patients; and when compared to the control group, comorbidities, severity of infection, and laboratory investigations were not statistically different. Hospitalization at the first infection was higher, but not statistically different when compared to the control group (P = 0.093). CONCLUSION: COVID-19 reinfection is rare and does not carry a higher risk of severe disease. Further studies are required, especially with the continuously newly emerging variants, with the unpredictable risk of reinfection.

5.
J Infect Public Health ; 15(5): 573-577, 2022 May.
Article in English | MEDLINE | ID: covidwho-1773509

ABSTRACT

BACKGROUND: Two vaccines for COVID-19 have been approved and administered in the Kingdom of Saudi Arabia (KSA); Pfizer-BioNtech BNT162b2 and AstraZeneca-Oxford AZD1222 vaccines. The purpose of this study was to describe the real-world data on the outcome of single dose of these COVID-19 vaccines in a large cohort in KSA and to analyse demographics and co-morbidities as risk factors for infection post one-dose vaccination. METHODS: In this prospective cohort study, a total of 18,543 subjects received one dose of either of the vaccines at a vaccination centre in KSA, and were followed up for three to eight months. Data were collected from three sources; clinical data from medical records, adverse events (AEs) from a self-reporting system, and COVID-19 infection data from the national databases. The study was conducted during the pandemic restrictions on travel, mobility, and social interactions. RESULTS: The median age of participants was 33 years with an average body mass index of 27.3. The majority were males (60.1%). Results showed that 92.17% of the subjects had no COVID-19 infection post-vaccination as infection post-vaccination was documented for 1452 (7.83%). Diabetes mellitus 03), organ transplantation (p = 0.02), and obesity (p < 0.01) were associated with infection post-vaccination. Unlike vaccine type, being Saudi, male, or obese was associated with the occurrence breakthrough infections more than other parameters. AEs included injection site pain, fatigue, fever, myalgia, headache and was reported by 5.8% of the subjects. CONCLUSION: Single dose COVID-19 vaccines showed a protection rate of 92.17% up to eight months follow-up in this cohort. This rate in AZD1222 was higher than what have been previously reported in effectiveness studies and clinical trials. Obese, male, and Saudi were at higher risk of contracting the infection post-vaccination, Saudi and male might have more social interaction with the public when mobility and social interactions were limited during the pandemic. Side effects and AEs were within what has been reported in clinical trials.


Subject(s)
COVID-19 , Vaccines , Adult , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , Female , Follow-Up Studies , Humans , Male , Obesity/epidemiology , Prospective Studies , SARS-CoV-2 , Saudi Arabia/epidemiology
6.
Clin Microbiol Infect ; 28(4): 602-608, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1708470

ABSTRACT

OBJECTIVE: To evaluate whether favipiravir reduces the time to viral clearance as documented by negative RT-PCR results for severe acute respiratory syndrome coronavirus 2 in mild cases of coronavirus disease 2019 (COVID-19) compared to placebo. METHODS: In this randomized, double-blinded, multicentre, and placebo-controlled trial, adults with PCR-confirmed mild COVID-19 were recruited in an outpatient setting at seven medical facilities across Saudi Arabia. Participants were randomized in a 1:1 ratio to receive either favipiravir 1800 mg by mouth twice daily on day 1 followed by 800 mg twice daily (n = 112) or a matching placebo (n = 119) for a total of 5 to 7 days. The primary outcome was the effect of favipiravir on reducing the time to viral clearance (by PCR test) within 15 days of starting the treatment compared to the placebo group. The trial included the following secondary outcomes: symptom resolution, hospitalization, intensive care unit admissions, adverse events, and 28-day mortality. RESULTS: Two hundred thirty-one patients were randomized and began the study (median age, 37 years; interquartile range (IQR): 32-44 years; 155 [67%] male), and 112 (48.5%) were assigned to the treatment group and 119 (51.5%) into the placebo group. The data and safety monitoring board recommended stopping enrolment because of futility at the interim analysis. The median time to viral clearance was 10 days (IQR: 6-12 days) in the favipiravir group and 8 days (IQR: 6-12 days) in the placebo group, with a hazard ratio of 0.87 for the favipiravir group (95% CI 0.571-1.326; p = 0.51). The median time to clinical recovery was 7 days (IQR: 4-11 days) in the favipiravir group and 7 days (IQR: 5-10 days) in the placebo group. There was no difference between the two groups in the secondary outcome of hospital admission. There were no drug-related severe adverse events. CONCLUSION: In this clinical trial, favipiravir therapy in mild COVID-19 patients did not reduce the time to viral clearance within 15 days of starting the treatment.


Subject(s)
COVID-19 , Adult , Amides/therapeutic use , COVID-19/drug therapy , Double-Blind Method , Humans , Male , Pyrazines/adverse effects , Treatment Outcome
7.
J Infect Public Health ; 15(1): 36-41, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1603449

ABSTRACT

INTRODUCTION: Immunomodulators, including dexamethasone (DEX), have been recommended by the Infectious Disease Society of America (IDSA) to treat moderate, severe, and critical COVID-19. Tocilizumab (TCZ) was added to the treatment recommendations based on recent data from two large randomized controlled trials and its potential synergistic effect with DEX. METHOD: We included adult patients admitted from June until October 2020 with a PCR confirmed SARS-CoV-2 infection. 135 patients with severe to critical COVID-19 and received TCZ and/or corticosteroid or DEX were retrospectively evaluated and followed until hospital discharge or death. RESULTS: The cohort was divided into two different groups of patients; TCZ group received TCZ ± corticosteroid, N = 100 and DEX group received DEX, N = 35. Groups were analyzed for hospital mortality. The rate of hospital mortality was 36% in TCZ and 37% in the DEX group, p = 0.91. Age of 60 years and above was associated with higher mortality rate with OR = 1.030 and 95% CI = (1.004, 1.057). More than 50% of patients required MV in both groups. Development of bacterial or fungal infection post immunomodulator were similar in TCZ and DEX groups, 29% vs. 31.4%. CONCLUSION: Our study revealed that age of 60 years and above is the only factor associated with higher mortality rate regardless of the type of immunomodulator therapy. Findings of this study also revealed the lack of synergistic effect between TCZ and DEX on the hospital mortality.


Subject(s)
COVID-19 , Adrenal Cortex Hormones/therapeutic use , Adult , Antibodies, Monoclonal, Humanized , COVID-19/drug therapy , Dexamethasone/therapeutic use , Humans , Middle Aged , Retrospective Studies , SARS-CoV-2
8.
Lancet Microbe ; 3(1): e11-e20, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1505678

ABSTRACT

BACKGROUND: ChAdOx1-vectored vaccine candidates against several pathogens have been developed and tested in clinical trials and ChAdOx1 nCoV-19 has now been licensed for emergency use for COVID-19. We assessed the safety and immunogenicity of the ChAdOx1 MERS vaccine in a phase 1b trial in healthy Middle Eastern adults. METHOD: MERS002 is an open-label, non-randomised, dose-escalation, phase 1b trial. Healthy Middle Eastern adults aged 18-50 years were included in the study. ChAdOx1 MERS was administered as a single intramuscular injection into the deltoid muscle of the non-dominant arm at three different dose groups: 5·0 × 109 viral particles in a low-dose group, 2·5 × 1010 viral particles in an intermediate-dose group, and 5·0 × 1010 viral particles in a high-dose group. The primary objective was to assess the safety and tolerability of ChAdOx1 MERS, measured by the occurrence of solicited and unsolicited adverse events after vaccination for up to 28 days and occurrence of serious adverse events up to 6 months. The study is registered with ClinicalTrials.gov, NCT04170829. FINDINGS: Between Dec 17, 2019, and June 1, 2020, 24 participants were enrolled (six to the low-dose, nine to the intermediate-dose, and nine to the high-dose group) and received a dose; 23 were available for follow-up at 6 months. The one dose of ChAdOx1 MERS vaccine was well tolerated with no serious adverse event reported during the 6 months of follow-up. Most adverse events were mild (67, 74%) and moderate (17, 19%). Six (7%) severe adverse events were reported by two participants in the intermediate-dose group (two feverish, two headache, one joint pain, and one muscle pain). Pain at the injection site was the most common local and overall adverse event, reported by 15 (63%) of the 24 participants. The most common systemic adverse event was headache, reported by 14 (58%), followed by muscle pain reported by 13 (54%). The vaccine induced both antibody and T cell immune responses in all volunteers; antibodies peaked at day 28 and T cell responses peaked at day 14; and continued until the end of follow-up at 6 months. INTERPRETATION: The acceptable safety and immunogenicity data from this phase 1b trial of ChAdOx1 MERS vaccine candidate in Healthy Middle Eastern adults, combined with previous safety and immunogenicity data from a trial in the UK, support selecting the ChAdOx1 MERS vaccine for advancement into phase 2 clinical evaluation. FUNDING: UK Department of Health and Social Care, using UK Aid funding, managed by the UK National Institute for Health Research; and King Abdullah International Medical Research Center.


Subject(s)
COVID-19 , Adult , Antibodies, Viral , COVID-19/prevention & control , Coronavirus Infections/prevention & control , Headache , Humans , Immunogenicity, Vaccine , Myalgia , Vaccines, DNA , Viral Vaccines
9.
J Multidiscip Healthc ; 14: 2017-2033, 2021.
Article in English | MEDLINE | ID: covidwho-1346356

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, in late 2019 and created a global pandemic that overwhelmed healthcare systems. COVID-19, as of July 3, 2021, yielded 182 million confirmed cases and 3.9 million deaths globally according to the World Health Organization. Several patients who were initially diagnosed with mild or moderate COVID-19 later deteriorated and were reclassified to severe disease type. OBJECTIVE: The aim is to create a predictive model for COVID-19 ventilatory support and mortality early on from baseline (at the time of diagnosis) and routinely collected data of each patient (CXR, CBC, demographics, and patient history). METHODS: Four common machine learning algorithms, three data balancing techniques, and feature selection are used to build and validate predictive models for COVID-19 mechanical requirement and mortality. Baseline CXR, CBC, demographic, and clinical data were retrospectively collected from April 2, 2020, till June 18, 2020, for 5739 patients with confirmed PCR COVID-19 at King Abdulaziz Medical City in Riyadh. However, of those patients, only 1508 and 1513 have met the inclusion criteria for ventilatory support and mortalilty endpoints, respectively. RESULTS: In an independent test set, ventilation requirement predictive model with top 20 features selected with reliefF algorithm from baseline radiological, laboratory, and clinical data using support vector machines and random undersampling technique attained an AUC of 0.87 and a balanced accuracy of 0.81. For mortality endpoint, the top model yielded an AUC of 0.83 and a balanced accuracy of 0.80 using all features with balanced random forest. This indicates that with only routinely collected data our models can predict the outcome with good performance. The predictive ability of combined data consistently outperformed each data set individually for intubation and mortality. For the ventilator support, chest X-ray severity annotations alone performed better than comorbidity, complete blood count, age, or gender with an AUC of 0.85 and balanced accuracy of 0.79. For mortality, comorbidity alone achieved an AUC of 0.80 and a balanced accuracy of 0.72, which is higher than models that use either chest radiograph, laboratory, or demographic features only. CONCLUSION: The experimental results demonstrate the practicality of the proposed COVID-19 predictive tool for hospital resource planning and patients' prioritization in the current COVID-19 pandemic crisis.

10.
Infect Dis Ther ; 10(4): 2291-2307, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1328677

ABSTRACT

INTRODUCTION: Antiviral drugs have shown limited effectiveness in treating patients with coronavirus disease 2019 (COVID-19). We aimed to assess the effects of a favipiravir and hydroxychloroquine combination on treating moderate-to-severe COVID-19 patients. METHODS: An investigator-initiated, multicenter, open-label, randomized trial at nine hospitals. Eligible patients were adults with moderate-to-severe COVID-19 defined as oxygen saturation (SaO2) of ≤ 94% while breathing ambient air or significant clinical symptoms with chest x-ray changes requiring hospital admission. Randomization was in a 1:1 ratio to receive standard care (control group) or standard care plus favipiravir and hydroxychloroquine. The primary outcome was time to clinical improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital within 14 days. Analyses were done in an intention-to-treat population. RESULTS: From May 2020 to Jan 2021, 254 patients were enrolled; 129 were assigned to standard of care and 125 to the treatment. The mean age was 52 (± 13) years, and 103 (41%) were women. At randomization, six patients were on invasive mechanical ventilation, 229 (90.15%) were requiring supplemental oxygen only (with or without non-invasive ventilation), and 19 (7.48%) were receiving neither. The time to clinical improvement was not significantly different between the groups: median of 9 days in the treatment group and 7 days in the control group (HR: 0.845; 95% CI 0.617-1.157; p-value = 0.29). The 28-day mortality was not significantly different between the groups (7.63% treatment) vs. (10.32% control); p-value = 0.45. The most prevalent adverse events were headache, elevation in ALT, and the prolonged QTc interval in the treatment group. CONCLUSION: The combination of favipiravir and hydroxychloroquine did not result in a statistically significant clinical benefit in patients with moderate-to-severe COVID-19. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04392973).

11.
BMJ Open ; 11(4): e047495, 2021 04 14.
Article in English | MEDLINE | ID: covidwho-1186293

ABSTRACT

INTRODUCTION: A novel coronavirus, designated SARS-CoV-2, caused an international outbreak of a respiratory illness, termed COVID-19 in December 2019. There is a lack of specific therapeutic agents based on evidence for this novel coronavirus infection; however, several medications have been evaluated as a potential therapy. Therapy is required to treat symptomatic patients and decrease the virus carriage duration to limit the communitytransmission. METHODS AND ANALYSIS: We hypothesise that patients with mild COVID-19 treated with favipiravir will have a shorter duration of time to virus clearance than the control group. The primary outcome is to evaluate the effect of favipiravir on the timing of the PCR test conversion from positive to negative within 15 days after starting the medicine.Adults (>18 years, men or nonpregnant women, diagnosed with mild COVID-19 within 5 days of disease onset) are being recruited by physicians participating from the Ministry of National Guard Health Affairs and the Ministry of Health ethics committee approved primary healthcare centres. This double-blind, randomised trial comprises three significant parts: screening, treatment and a follow-up period. The treating physician and patients are blinded. Eligible participants are randomised in a 1:1 ratio to either the therapy group (favipiravir) or a control group (placebo) with 1800 mg by mouth two times per day for the first day, followed by 800 mg two times per day for 4-7 days. Serial nasopharyngeal/oropharyngeal swab samples are obtained on day 1 (5 days before therapy). On day5±1 day, 10±1 day, 15±2 days, extra nasopharyngeal/oropharyngeal PCR COVID-19 samples are requested.The primary analysis population for evaluating both the efficacy and safety outcomes will be a modified intention to treat population. Anticipating a 10% dropout rate, we expect to recruit 288 subjects per arm. The results assume that the hazard ratio is constant throughout the study and that the Cox proportional hazard regression is used to analyse the data. ETHICS AND DISSEMINATION: The study was approved by the King Abdullah International Medical Research Centre Institutional Review Board (28 April 2020) and the Ministry of Health Institutional Review Board (1 July 2020). Protocol details and any amendments will be reported to https://clinicaltrials.gov/ct2/show/NCT04464408. The results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: National Clinical Trial Registry (NCT04464408).


Subject(s)
Amides/therapeutic use , COVID-19/drug therapy , Pyrazines/therapeutic use , Adult , Female , Humans , Male , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Treatment Outcome
12.
Genomics ; 113(4): 1733-1741, 2021 07.
Article in English | MEDLINE | ID: covidwho-1171554

ABSTRACT

Interferon-induced membrane proteins (IFITM) 3 gene variants are known risk factor for severe viral diseases. We examined whether IFITM3 variant may underlie the heterogeneous clinical outcomes of SARS-CoV-2 infection-induced COVID-19 in large Arab population. We genotyped 880 Saudi patients; 93.8% were PCR-confirmed SARS-CoV-2 infection, encompassing most COVID-19 phenotypes. Mortality at 90 days was 9.1%. IFITM3-SNP, rs12252-G allele was associated with hospital admission (OR = 1.65 [95% CI; 1.01-2.70], P = 0.04]) and mortality (OR = 2.2 [95% CI; 1.16-4.20], P = 0.01). Patients less than 60 years old had a lower survival probability if they harbor this allele (log-rank test P = 0.002). Plasma levels of IFNγ were significantly lower in a subset of patients with AG/GG genotypes than patients with AA genotype (P = 0.00016). Early identification of these individuals at higher risk of death may inform precision public health response.


Subject(s)
COVID-19/genetics , Genetic Predisposition to Disease , Membrane Proteins/genetics , RNA-Binding Proteins/genetics , SARS-CoV-2/genetics , Adult , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/virology , Female , Genetic Association Studies , Genotype , Humans , Interferons/genetics , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , SARS-CoV-2/pathogenicity
13.
Trials ; 21(1): 904, 2020 Oct 31.
Article in English | MEDLINE | ID: covidwho-901915

ABSTRACT

OBJECTIVES: The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, we want to prove the clinical effectiveness of the combination as therapy. TRIAL DESIGN: This is an Open label, multicenter, randomized controlled clinical trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. It is a multicenter trial that will compare Favipiravir plus Hydroxychloroquine combination (experimental arm) to a control arm. PARTICIPANTS: All study procedures will be conducted in eight centres in Saudia Arabia: King Abdulaziz Medical City National Guard Health Affairs in Riyadh. King Abdulaziz Hospital - Al Ahsa, Saudi Arabia AlMadina General Hospital, Madnia, Saudi Arabia Al-Qatif Central Hospital, Saudi Arabia Imam Abdulrahman Al Faisal Hospital, Dammam, Saudi Arabia King Abdulaziz Medical City, Jeddah, Saudi Arabia King Abdulaziz Hospital, Makkah, Saudi Arabia Imam Abdulrahman Alfaisal Hospital, Riyadh, Saudi Arabia Inclusion Criteria • Should be at least 18 years of age, • Male or nonpregnant female, • Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection. • Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions).. • Moderate or Severe COVID-19, defined as oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or significant clinical symptoms that require hospital admission. • patients had to be enrolled within 10 days of disease onset. Exclusion Criteria • Patients who are pregnant or breastfeeding. • Will be transferred to a non-study site hospital or discharged from hospital within 72 hours. • Known sensitivity/allergy to hydroxychloroquine or Favipiravir • Current use of hydroxychloroquine for another indication • Prior diagnosis of retinopathy • Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency • Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit), HIV. • The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues). • Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission • Patient with irregular rhythm • Patient with a history of heart attack (myocardial infarction) • Patient with a family history of sudden death from heart attack before the age of 50 • Take other drugs that can cause prolonged QT interval • Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to another agent or adjusted while using the investigational drug • Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract. INTERVENTION AND COMPARATOR: The treatment intervention would be for a maximum of 10 days from randomization and it would be as follows: Favipiravir for 10 days: Administer 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (total days of therapy is 10 days) Hydroxychloroquine for 5 days: (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily. Reference Comparator Therapy: Standard of care is defined as: Treatment that is accepted by medical experts as a proper treatment for Covid-19 disease. Standard care comprised of, as necessary, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, extracorporeal membrane oxygenation (ECMO), and antiviral therapy except Favipiravir. Also, it may include intravenous fluids and medications for symptoms relief . MAIN OUTCOMES: The primary endpoint is the time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first (14 days from Randomization). RANDOMISATION: Eligible participants will be randomized in a 1:1 ratio to either the combination group (Favipiravir and Hydroxychloroquine) or a control group. The patients will be randomized utilizing Web based data entry System with a stratification based on the centre and the ICU admission. BLINDING (MASKING): This is an Open label study and only the analyst will be blinded during the study conduct. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Under the classical two arm parallel design the total effective sample sizes needed is 472 subjects (236 subjects per group). TRIAL STATUS: Protocol version 3.1 (dated 11 Aug 2020), and currently recruitment is ongoing. The date recruitment started was May 21, 2020 and the investigators anticipate the trial will finish recruiting by the end of December 2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04392973 , 19 May 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Amides/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Pyrazines/therapeutic use , Amides/adverse effects , Antiviral Agents/adverse effects , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Drug Therapy, Combination , Female , Host-Pathogen Interactions , Humans , Hydroxychloroquine/adverse effects , Inpatients , Male , Multicenter Studies as Topic , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Pyrazines/adverse effects , Randomized Controlled Trials as Topic , SARS-CoV-2 , Saudi Arabia , Time Factors , Treatment Outcome
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