Dataset Information

Hydroxychloroquine versus Azithromycin for Hospitalized Patients with Suspected or Confirmed COVID-19 (HAHPS). Protocol for a Pragmatic, Open-Label, Active Comparator Trial.

ABSTRACT: Coronavirus disease (COVID-19) is a potentially fatal illness with no proven therapy beyond excellent supportive care. Treatments are urgently sought. Adaptations to traditional trial logistics and design to allow rapid implementation, evaluation of trials within a global trials context, flexible interim monitoring, and access outside traditional research hospitals (even in settings where formal placebos are unavailable) may be helpful. Thoughtful adaptations to traditional trial designs, especially within the global context of related studies, may also foster collaborative relationships among government, community, and the research enterprise. Here, we describe the protocol for a pragmatic, active comparator trial in as many as 300 patients comparing two current "off-label" treatments for COVID-19-hydroxychloroquine and azithromycin-in academic and nonacademic hospitals in Utah. We developed the trial in response to local pressures for widespread, indiscriminate off-label use of these medications. We used a hybrid Bayesian-frequentist design for interim monitoring to allow rapid, contextual assessment of the available evidence. We also developed an inference grid for interpreting the range of possible results from this trial within the context of parallel trials and prepared for a network meta-analysis of the resulting data. This trial was prospectively registered (ClinicalTrials.gov Identifier: NCT04329832) before enrollment of the first patient.Clinical trial registered with www.clinicaltrials.gov (NCT04329832).

SUBMITTER: Brown SM

PROVIDER: S-EPMC7393787 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Hydroxychloroquine versus Azithromycin for Hospitalized Patients with Suspected or Confirmed COVID-19 (HAHPS). Protocol for a Pragmatic, Open-Label, Active Comparator Trial.

Brown Samuel M SM Peltan Ithan D ID Webb Brandon B Kumar Naresh N Starr Nathan N Grissom Colin C Buckel Whitney R WR Srivastava Raj R Harris Estelle S ES Leither Lindsay M LM Johnson Stacy A SA Paine Robert R Greene Tom T

Annals of the American Thoracic Society 20200801 8

Coronavirus disease (COVID-19) is a potentially fatal illness with no proven therapy beyond excellent supportive care. Treatments are urgently sought. Adaptations to traditional trial logistics and design to allow rapid implementation, evaluation of trials within a global trials context, flexible interim monitoring, and access outside traditional research hospitals (even in settings where formal placebos are unavailable) may be helpful. Thoughtful adaptations to traditional trial designs, especi ...[more]

PMID: 32425051

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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:BackgroundOral antipyretics are commonly used to treat pediatric patients who develop fevers. However, patients presenting to the emergency department or undergoing surgery are frequently unable to tolerate oral antipyretics. Rectal formulations are available; however, this route of administration is unpredictable. The main objectives of this randomized controlled study was to evaluate the efficacy and safety of single or multiple doses of intravenous ibuprofen to acetaminophen (oral or suppository) in pediatric patients with fever and to assess plasma ibuprofen concentrations.MethodsThis multi-center study was conducted in hospitalized patients, ≤ 16 years, with a new onset of fever ≥ 38.3°C. Patients were randomly assigned to receive either 10 mg/kg intravenous ibuprofen or acetaminophen. Study drug was administered at hour 0, and thereafter every 4 h as needed, up to 5 days. The primary outcome was to evaluate the effect of a single dose of intravenous ibuprofen compared to acetaminophen in reducing temperature in the first 2 h after administration. Data were compared using an analysis of variance model for continuous measurements and Cochran-Mantel-Haenszel test of general association for categorical data. A two-sided testing was used and a p-value ≤ 0.05 was considered significant.ResultsA total of 103 patients received study medication. Intravenous ibuprofen resulted in a greater reduction in temperature as measured by the area under the change from baseline at 2 h (p = 0.005) and 4 h (<0.001); in a greater reduction in change from baseline temperature compared to treatment with acetaminophen, and it reduced fever throughout a 24 h dosing period. There were no differences in safety parameters or serious adverse events.ConclusionsA single 10 mg/kg dose of intravenous ibuprofen provided a significant reduction of temperature for febrile pediatric patients compared to those that received 10 mg/kg acetaminophen at 2 h and 4 h post-treatment. A reduction in temperature was also demonstrated over 24 h; however the reduction was not considered statically significant. Intravenous ibuprofen provides an effective option for reducing fever in hospitalized pediatric patients.Trial registrationThe study was registered on ClinicalTrials.gov on 26 October 2009, Study Identifier: NCT01002573.

Project description:Summary Background By October 30, 2022, 76,871 cases of mpox were reported worldwide, with 20,614 cases in Latin America. This study reports characteristics of a case series of suspected and confirmed mpox cases at a referral infectious diseases center in Rio de Janeiro, Brazil. Methods This was a single-center, prospective, observational cohort study that enrolled all patients with suspected mpox between June 12 and August 19, 2022. Mpox was confirmed by a PCR test. We compared characteristics of confirmed and non-confirmed cases, and among confirmed cases according to HIV status using distribution tests. Kernel estimation was used for exploratory spatial analysis. Findings Of 342 individuals with suspected mpox, 208 (60.8%) were confirmed cases. Compared to non-confirmed cases, confirmed cases were more frequent among individuals aged 30–39 years, cisgender men (96.2% vs. 66.4%; p < 0.0001), reporting recent sexual intercourse (95.0% vs. 69.4%; p < 0.0001) and using PrEP (31.6% vs. 10.1%; p < 0.0001). HIV (53.2% vs. 20.2%; p < 0.0001), HCV (9.8% vs. 1.1%; p = 0.0046), syphilis (21.2% vs. 16.3%; p = 0.43) and other STIs (33.0% vs. 21.6%; p = 0.042) were more frequent among confirmed mpox cases. Confirmed cases presented more genital (77.3% vs. 39.8%; p < 0.0001) and anal lesions (33.1% vs. 11.5%; p < 0.0001), proctitis (37.1% vs. 13.3%; p < 0.0001) and systemic signs and symptoms (83.2% vs. 64.5%; p = 0.0003) than non-confirmed cases. Compared to confirmed mpox HIV-negative, HIV-positive individuals were older, had more HCV coinfection (15.2% vs. 3.7%; p = 0.011), anal lesions (45.7% vs. 20.5%; p < 0.001) and clinical features of proctitis (45.2% vs. 29.3%; p = 0.058). Interpretation Mpox transmission in Rio de Janeiro, Brazil, rapidly evolved into a local epidemic, with sexual contact playing a crucial role in its dynamics and high rates of coinfections with other STI. Preventive measures must address stigma and social vulnerabilities. Funding Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (INI-Fiocruz).

Project description:BackgroundThe use of rosuvastatin plus colchicine and emtricitabine/tenofovir in hospitalized patients with SARS-CoV-2 disease (COVID-19) has not been assessed. The objective of this study was to assess the effectiveness and safety of rosuvastatin plus colchicine, emtricitabine/tenofovir, and their combined use in these patients.MethodsThis was a randomized, controlled, open-label, multicentre, parallel, pragmatic study conducted in six referral hospitals in Bogotá, Colombia. The study enrolled hospitalized patients over 18 years of age with a confirmed diagnosis of COVID-19 complicated with pneumonia, not on chronic treatment with the study medications, and with no contraindications for their use. Patients were assigned 1:1:1:1. 1) emtricitabine with tenofovir disoproxil fumarate (FTC/TDF, 200/300 mg given orally for 10 days); 2) colchicine plus rosuvastatin (COLCH+ROSU, 0.5 mg and 40 mg given orally for 14 days); 3) emtricitabine with tenofovir disoproxil plus colchicine and rosuvastatin at the same doses and for the same period of time (FTC/TDF+COLCH+ROSU); or 4) the Colombian consensus standard of care, including a corticosteroid (SOC). The primary endpoint was 28-day all-cause mortality. A modified intention-to-treat analysis was used together with a usefulness analysis to determine which could be the best treatment. The trial was registered at ClinicalTrials.gov: NCT04359095.FindingsOut of 994 candidates considered between August 2020 and March 2021, 649 (65.3%) patients agreed to participate and were enrolled in this study; among them, 633 (97.5%) were included in the analysis. The mean age was 55.4 years (SD ± 12.8 years), and 428 (68%) were men; 28-day mortality was significantly lower in the FTC/TDF+COLCH+ROSUV group than in the SOC group, 10.7% (17/159) vs. 17.4% (28/161) (hazard ratio [HR] 0.53; 95% CI 0.29 to 0.96). Mortality in the FTC/TDF group was 13.8% (22/160, HR 0.68, 95% CI 0.39 to 1.20) and 14.4% in the COLCH+ROSU group (22/153) (HR 0.78, 95% CI 0.44 to 1.36). A lower need for invasive mechanical ventilation was observed in the FTC/TDF+COLCH+ROSUV group than in the SOC group (risk difference [RD] - 0.08, 95% CI 0.11 to 0.04). Three patients presented severe adverse events, one severe diarrhoea in the COLCH+ROSU and one in the FTC/TDF+COLCH+ROSU group and one general exanthema in the FTC/TDF group.InterpretationThe combined use of FTC/TDF+COLCH+ROSU reduces the risk of 28-day mortality and the need for invasive mechanical ventilation in hospitalized patients with pulmonary compromise from COVID-19. More randomized controlled trials are needed to compare the effectiveness and cost of treatment with this combination versus other drugs that have been shown to reduce mortality from SARS-CoV-2 infection and its usefulness in patients with chronic statin use.

Dataset Information

Hydroxychloroquine versus Azithromycin for Hospitalized Patients with Suspected or Confirmed COVID-19 (HAHPS). Protocol for a Pragmatic, Open-Label, Active Comparator Trial.

Publications

Hydroxychloroquine versus Azithromycin for Hospitalized Patients with Suspected or Confirmed COVID-19 (HAHPS). Protocol for a Pragmatic, Open-Label, Active Comparator Trial.

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