Dataset Information

Rationale and Design of the COVID-19 Outpatient Prevention Evaluation (COPE - Coalition V) Randomized Clinical Trial: Hydroxychloroquine vs. Placebo in Non-Hospitalized Patients.

ABSTRACT:

Background

Despite the need for targeting specific therapeutic options for coronavirus disease 2019 (COVID-19), there has been no evidence of effectiveness of any specific treatment for the outpatient clinical setting. There are few randomized studies evaluating hydroxychloroquine (HCQ) in non-hospitalized patients. These studies indicate no benefit from the use of HCQ, but they assessed different primary outcomes and presented important biases for outcome evaluation.

Objective

To evaluate if HCQ may prevent hospitalization due to COVID-19 compared to a matching placebo.

Methods

The COVID-19 Outpatient Prevention Evaluation (COPE) study is a pragmatic, randomized, double-blind, placebo-controlled clinical trial evaluating the use of HCQ (800 mg on day 1 and 400 mg from day 2 to day 7) or matching placebo for the prevention of hospitalization due to COVID-19 in early non-hospitalized confirmed or suspected cases. Inclusion criteria are adults (≥ 18 years) seeking medical care with mild symptoms of COVID-19, with randomization ≤ 7 days after symptom onset, without indication of hospitalization at study screening, and with at least one risk factor for complication (> 65 years; hypertension; diabetes mellitus; asthma; chronic obstructive pulmonary disease or other chronic lung diseases; smoking; immunosuppression; or obesity). All hypothesis tests will be two-sided. A p-value < 0.05 will be considered statistically significant in all analyses. Clinicaltrials.gov: NCT04466540.

Results

Clinical outcomes will be centrally adjudicated by an independent clinical event committee blinded to the assigned treatment groups. The primary efficacy endpoint will be assessed following the intention-to-treat principle.

Conclusion

This study has the potential to reliably answer the scientific question of HCQ use in outpatients with COVID-19. To our knowledge, this is the largest trial evaluating HCQ in non-hospitalized individuals with COVID-19.

SUBMITTER: Oliveira Junior HA

PROVIDER: S-EPMC8856682 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Rationale and Design of the COVID-19 Outpatient Prevention Evaluation (COPE - Coalition V) Randomized Clinical Trial: Hydroxychloroquine vs. Placebo in Non-Hospitalized Patients.

Oliveira Junior Haliton Alves de HA Ferri Cleusa P CP Boszczowski Icaro I Oliveira Gustavo B F GBF Cavalcanti Alexandre B AB Rosa Regis G RG Lopes Renato D RD Azevedo Luciano C P LCP Veiga Viviane C VC Berwanger Otavio O Avezum Álvaro Á

Arquivos brasileiros de cardiologia 20220201 2

<h4>Background</h4>Despite the need for targeting specific therapeutic options for coronavirus disease 2019 (COVID-19), there has been no evidence of effectiveness of any specific treatment for the outpatient clinical setting. There are few randomized studies evaluating hydroxychloroquine (HCQ) in non-hospitalized patients. These studies indicate no benefit from the use of HCQ, but they assessed different primary outcomes and presented important biases for outcome evaluation.<h4>Objective</h4>To ...[more]

PMID: 35262569

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Project description:BackgroundPrevious Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in non-hospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers.MethodsWe conducted a multicenter, double-blind, RCT in 56 Brazilian sites. Adults with suspected or confirmed COVID-19 presenting with mild or moderate symptoms with ≤ 07 days prior to enrollment and at least one risk factor for clinical deterioration were randomised (1:1) to receive hydroxychloroquine 400 mg twice a day (BID) in the first day, 400 mg once daily (OD) thereafter for a total of seven days, or matching placebo. The primary outcome was hospitalisation due to COVID-19 at 30 days, which was assessed by an adjudication committee masked to treatment allocation and following the intention-to-treat (ITT) principle. An additional analysis was performed only in participants with SARS-CoV-2 infection confirmed by molecular or serology testing (modified ITT [mITT] analysis). This trial was registered at ClinicalTrials.gov, NCT04466540.FindingsFrom May 12, 2020 to July 07, 2021, 1372 patients were randomly allocated to hydroxychloroquine or placebo. There was no significant difference in the risk of hospitalisation between hydroxychloroquine and placebo groups (44/689 [6·4%] and 57/683 [8·3%], RR 0·77 [95% CI 0·52-1·12], respectively, p=0·16), and similar results were found in the mITT analysis with 43/478 [9·0%] and 55/471 [11·7%] events, RR 0·77 [95% CI 0·53-1·12)], respectively, p=0·17. To further complement our data, we conducted a meta-analysis which suggested no significant benefit of hydroxychloroquine in reducing hospitalisation among patients with positive testing (69/1222 [5·6%], and 88/1186 [7·4%]; RR 0·77 [95% CI 0·57-1·04]).InterpretationIn outpatients with mild or moderate forms of COVID-19, the use of hydroxychloroquine did not reduce the risk of hospitalisation compared to the placebo control. Our findings do not support the routine use of hydroxychloroquine for treatment of COVID-19 in the outpatient setting.FundingCOALITION COVID-19 Brazil and EMS.

Project description:RationaleThe COVID-19 pandemic struck an immunologically naïve, globally interconnected population. In the face of a new infectious agent causing acute respiratory failure for which there were no known effective therapies, rapid, often pragmatic trials were necessary to evaluate potential treatments, frequently starting with medications that are already marketed for other indications. Early in the pandemic, hydroxychloroquine and azithromycin were two such candidates.ObjectiveAssess the relative efficacy of hydroxychloroquine and azithromycin among hospitalized patients with COVID-19.MethodsWe performed a randomized clinical trial of hydroxychloroquine vs. azithromycin among hospitalized patients with COVID-19. Treatment was 5 days of study medication. The primary endpoint was the COVID Ordinal Outcomes scale at day 14. Secondary endpoints included hospital-, ICU-, and ventilator-free days at day 28. The trial was stopped early after enrollment of 85 patients when a separate clinical trial concluded that a clinically important effect of hydroxychloroquine over placebo was definitively excluded. Comparisons were made a priori using a proportional odds model from a Bayesian perspective.ResultsWe enrolled 85 patients at 13 hospitals over 11 weeks. Adherence to study medication was high. The estimated odds ratio for less favorable status on the ordinal scale for hydroxychloroquine vs. azithromycin from the primary analysis was 1.07, with a 95% credible interval from 0.63 to 1.83 with a posterior probability of 60% that hydroxychloroquine was worse than azithryomycin. Secondary outcomes displayed a similar, slight preference for azithromycin over hydroxychloroquine. QTc prolongation was rare and did not differ between groups. The twenty safety outcomes were similar between arms with the possible exception of post-randomization onset acute kidney injury, which was more common with hydroxychloroquine (15% vs. 0%). Patients in the hydroxychloroquine arm received remdesivir more often than in the azithromycin arm (19% vs. 2%). There was no apparent association between remdesivir use and acute kidney injury.ConclusionsWhile early termination limits the precision of our results, we found no suggestion of substantial efficacy for hydroxychloroquine over azithromycin. Acute kidney injury may be more common with hydroxychloroquine than azithromycin, although this may be due to the play of chance. Differential use of remdesivir may have biased our results in favor of hydroxychloroquine. Our results are consistent with conclusions from other trials that hydroxychloroquine cannot be recommended for inpatients with COVID-19; azithromycin may merit additional investigation.Clinical trial registrationThis trial was prospectively registered (NCT04329832) before enrollment of the first patient.

Project description:BackgroundRecent advances in the treatment algorithms of early breast cancer have markedly improved overall survival. However, anthracycline- and trastuzumab-associated cardiotoxicity may lead to dose-reduction or halt in potentially life-saving adjuvant cancer therapy. Early initiated neurohormonal blockade may prevent or attenuate the cardiotoxicity-induced reduction in cardiac function, but prior studies have been inconclusive. The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan has been shown to be superior to traditional treatment in heart failure with reduced ejection fraction, but its cardioprotective effects in the cardio-oncology setting remains to be tested.ObjectiveTo assess if sacubitril/valsartan given concomitantly with early breast cancer treatment regimens including anthracyclines, with or without trastuzumab, may prevent cardiac dysfunction.MethodsPRADA II is a randomized, placebo-controlled, double blind, multi-center, investigator-initiated clinical trial. Breast cancer patients from four university hospitals in Norway, scheduled to receive (neo-)adjuvant chemotherapy with epirubicin independently of additional trastuzumab/pertuzumab treatment, will be randomized 1:1 to sacubitril/valsartan or placebo. The target dose is 97/103 mg b.i.d. The patients will be examined with cardiovascular magnetic resonance (CMR), echocardiography, circulating cardiovascular biomarkers and functional testing at baseline, at end of anthracycline treatment and following 18 months after enrolment. The primary outcome measure of the PRADA II trial is the change in left ventricular ejection fraction (LVEF) by CMR from baseline to 18 months. Secondary outcomes include change in LV function by global longitudinal strain by CMR and echocardiography and change in circulating cardiac troponin concentrations.ResultsThe study is ongoing. Results will be published when the study is completed.ConclusionPRADA II is the first randomized, placebo-controlled study of sacubitril/valsartan in a cardioprotective setting during (neo-)adjuvant breast cancer therapy. It may provide new insight in prevention of cardiotoxicity in patients receiving adjuvant or neo-adjuvant therapy containing anthracyclines. Furthermore, it may enable identification of patients at higher risk of developing cardiotoxicity and identification of those most likely to respond to cardioprotective therapy.Trial registrationThe trial is registered in the ClinicalTrials.gov registry (identifier NCT03760588 ). Registered 30 November 2018.

Project description:BackgroundPrevious studies have demonstrated a high risk of arterial and venous thromboembolic events as a consequence of direct viral damage to endothelial cells by SARS-CoV-2 and a procoagulant milieu due to increased biomarkers, such as D-dimer, fibrinogen, and factor VIII. Although randomized controlled trials of antithrombotic therapies have been conducted in hospitalized patients, few have evaluated the role of thromboprophylaxis in an outpatient setting.ObjectiveTo assess whether antithrombotic prophylaxis with rivaroxaban reduces the risk of venous or arterial thrombotic events, invasive ventilatory support, and death in COVID-19 outpatients.MethodsThe COVID Antithrombotic Rivaroxaban Evaluation (CARE) study, a multicenter, randomized, open-label, controlled trial of rivaroxaban 10 mg once daily for 14 days or local standard treatment alone to prevent adverse outcomes, is registered in clinicaltrials.gov (NCT04757857). The inclusion criteria are adults with confirmed or suspected SARS-CoV-2 infection and mild or moderate symptoms without indication for hospitalization, within 7 days of symptom onset, and 1 risk factor for COVID-19 complication (> 65 years, hypertension, diabetes mellitus, asthma, chronic obstructive pulmonary disease or other chronic lung diseases, smoking, immunosuppression, or obesity). The primary composite endpoint, which includes venous thromboembolism, invasive mechanical ventilation, major acute cardiovascular events, and mortality within 30 days of randomization, will be assessed according to the intention-to-treat principle. All patients will provide informed consent. A significance level of 5% will be used for all statistical tests.ResultsMajor thrombotic and bleeding outcomes, hospitalizations, and deaths will be centrally adjudicated by an independent clinical events committee blinded to the assigned treatment groups.ConclusionThe CARE study will provide relevant and contemporary information about the potential role of thromboprophylaxis in outpatients with COVID-19.

Dataset Information

Rationale and Design of the COVID-19 Outpatient Prevention Evaluation (COPE - Coalition V) Randomized Clinical Trial: Hydroxychloroquine vs. Placebo in Non-Hospitalized Patients.

Background

Objective

Methods

Results

Conclusion

Publications

Rationale and Design of the COVID-19 Outpatient Prevention Evaluation (COPE - Coalition V) Randomized Clinical Trial: Hydroxychloroquine vs. Placebo in Non-Hospitalized Patients.

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