Dataset Information

Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial.

ABSTRACT:

Background

No effective oral therapy exists for early coronavirus disease 2019 (COVID-19).

Objective

To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients.

Design

Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668).

Setting

Internet-based trial across the United States and Canada (40 states and 3 provinces).

Participants

Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset.

Intervention

Oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo.

Measurements

Symptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days.

Results

Of 491 patients randomly assigned to a group, 423 contributed primary end point data. Of these, 341 (81%) had laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or epidemiologically linked exposure to a person with laboratory-confirmed infection; 56% (236 of 423) were enrolled within 1 day of symptoms starting. Change in symptom severity over 14 days did not differ between the hydroxychloroquine and placebo groups (difference in symptom severity: relative, 12%; absolute, -0.27 point [95% CI, -0.61 to 0.07 point]; P = 0.117). At 14 days, 24% (49 of 201) of participants receiving hydroxychloroquine had ongoing symptoms compared with 30% (59 of 194) receiving placebo (P = 0.21). Medication adverse effects occurred in 43% (92 of 212) of participants receiving hydroxychloroquine versus 22% (46 of 211) receiving placebo (P < 0.001). With placebo, 10 hospitalizations occurred (2 non-COVID-19-related), including 1 hospitalized death. With hydroxychloroquine, 4 hospitalizations occurred plus 1 nonhospitalized death (P = 0.29).

Limitation

Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages.

Conclusion

Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19.

Primary funding source

Private donors.

SUBMITTER: Skipper CP

PROVIDER: S-EPMC7384270 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial.

Skipper Caleb P CP Pastick Katelyn A KA Engen Nicole W NW Bangdiwala Ananta S AS Abassi Mahsa M Lofgren Sarah M SM Williams Darlisha A DA Okafor Elizabeth C EC Pullen Matthew F MF Nicol Melanie R MR Nascene Alanna A AA Hullsiek Kathy H KH Cheng Matthew P MP Luke Darlette D Lother Sylvain A SA MacKenzie Lauren J LJ Drobot Glen G Kelly Lauren E LE Schwartz Ilan S IS Zarychanski Ryan R McDonald Emily G EG Lee Todd C TC Rajasingham Radha R Boulware David R DR

Annals of internal medicine 20200716 8

<h4>Background</h4>No effective oral therapy exists for early coronavirus disease 2019 (COVID-19).<h4>Objective</h4>To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients.<h4>Design</h4>Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668).<h4>Setting</h4>Internet-based trial across the United States and Canada (40 states and 3 provinces).<h4>Participants</h4>Symptomatic, nonhospita ...[more]

PMID: 32673060

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Project description:BackgroundNirmatrelvir is an orally administered severe acute respiratory syndrome coronavirus 2 main protease (Mpro) inhibitor with potent pan-human-coronavirus activity in vitro.MethodsWe conducted a phase 2-3 double-blind, randomized, controlled trial in which symptomatic, unvaccinated, nonhospitalized adults at high risk for progression to severe coronavirus disease 2019 (Covid-19) were assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir (a pharmacokinetic enhancer) or placebo every 12 hours for 5 days. Covid-19-related hospitalization or death from any cause through day 28, viral load, and safety were evaluated.ResultsA total of 2246 patients underwent randomization; 1120 patients received nirmatrelvir plus ritonavir (nirmatrelvir group) and 1126 received placebo (placebo group). In the planned interim analysis of patients treated within 3 days after symptom onset (modified intention-to treat population, comprising 774 of the 1361 patients in the full analysis population), the incidence of Covid-19-related hospitalization or death by day 28 was lower in the nirmatrelvir group than in the placebo group by 6.32 percentage points (95% confidence interval [CI], -9.04 to -3.59; P<0.001; relative risk reduction, 89.1%); the incidence was 0.77% (3 of 389 patients) in the nirmatrelvir group, with 0 deaths, as compared with 7.01% (27 of 385 patients) in the placebo group, with 7 deaths. Efficacy was maintained in the final analysis involving the 1379 patients in the modified intention-to-treat population, with a difference of -5.81 percentage points (95% CI, -7.78 to -3.84; P<0.001; relative risk reduction, 88.9%). All 13 deaths occurred in the placebo group. The viral load was lower with nirmatrelvir plus ritonavir than with placebo at day 5 of treatment, with an adjusted mean difference of -0.868 log10 copies per milliliter when treatment was initiated within 3 days after the onset of symptoms. The incidence of adverse events that emerged during the treatment period was similar in the two groups (any adverse event, 22.6% with nirmatrelvir plus ritonavir vs. 23.9% with placebo; serious adverse events, 1.6% vs. 6.6%; and adverse events leading to discontinuation of the drugs or placebo, 2.1% vs. 4.2%). Dysgeusia (5.6% vs. 0.3%) and diarrhea (3.1% vs. 1.6%) occurred more frequently with nirmatrelvir plus ritonavir than with placebo.ConclusionsTreatment of symptomatic Covid-19 with nirmatrelvir plus ritonavir resulted in a risk of progression to severe Covid-19 that was 89% lower than the risk with placebo, without evident safety concerns. (Supported by Pfizer; ClinicalTrials.gov number, NCT04960202.).

Project description:BackgroundCoronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown.MethodsWe conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days.ResultsWe enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was -2.4 percentage points (95% confidence interval, -7.0 to 2.2; P = 0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported.ConclusionsAfter high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668.).

Project description:BackgroundCurrent strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking.MethodsWe conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days.ResultsThe analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported.ConclusionsPostexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.).

Project description:Probenecid is an orally bioavailable, uricosuric agent that was first approved in 1951 for the treatment of gout, but was later found to have potent, broad-spectrum antiviral activity against several respiratory viruses including SARS-CoV-2. We conducted a phase 2 randomized, placebo-controlled, single-blind, dose-range finding study in non-hospitalized patients with symptomatic, mild-to-moderate COVID-19. Patients were randomly assigned in a 1:1:1 ratio to receive either 500 mg of probenecid, 1000 mg of probenecid, or a matching placebo every 12 h for five days. The patients' COVID-19 viral load hospitalization, or death from any cause through day 28, as well as safety, were evaluated. COVID-19-related symptoms were assessed at baseline, and on days 3, 5, 10, 15, and 28. The primary endpoints of the study were time to first negative SARS-CoV-2 viral test (or viral clearance) and the proportion of patients that were symptom-free at day 5. A total of 75 patients were randomized, with 25 patients in each group. All of the patients completed the study as planned with no hospitalizations or deaths being reported. The median time to viral clearance was significantly shorter for the probenecid 1000 mg group than for placebo (7 days vs. 11 days, respectively; p < 0.0001), and for the probenecid 500 mg group versus placebo (9 days vs. 11 days, respectively; p < 0.0001). In addition, the median time to viral clearance was significantly shorter for the probenecid 1000 mg group than for the probenecid 500 mg group (7 days vs. 9 days, respectively; p < 0.0001). All patients reported at least one COVID-19-related symptom on days 3 and 5; however, on day 10, a significantly greater proportion of patients receiving probenecid 1000 mg reported the complete resolution of symptoms versus placebo (68% vs. 20%, respectively; p = 0.0006), as well as for those receiving probenecid 500 mg versus placebo (56% vs. 20%, respectively, p = 0.0087). The incidence of adverse events during treatment was similar across all groups for any adverse event, and was 12%. All events were mild with no serious adverse events reported and no discontinuations due to an adverse event. The treatment of patients with symptomatic, mild-to-moderate COVID-19 with probenecid resulted in a significant, dose-dependent decrease in the time to viral clearance and a significantly higher proportion of patients reporting complete symptom resolution by day 10. (Supported by TrippBio; ClinicalTrials.gov number, NCT05442983 and Clinical Trials Registry India number CTRI/2022/07/043726).

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Dataset Information

Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial.

Background

Objective

Design

Setting

Participants

Intervention

Measurements

Results

Limitation

Conclusion

Primary funding source

Publications

Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial.

Similar Datasets

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