Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
1.
JAMA ; 326(17): 1703-1712, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1525396

ABSTRACT

Importance: Acutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. Objective: To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. Design, Setting, and Participants: The ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m2. Interventions: Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. Results: On June 18, 2021, the trial data and safety monitoring board recommended early termination because of lower than anticipated event rates; at that time, 657 symptomatic outpatients with COVID-19 had been randomized (median age, 54 years [IQR, 46-59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar. Conclusions and Relevance: Among symptomatic clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome. However, the study was terminated after enrollment of 9% of participants because of an event rate lower than anticipated. Trial Registration: ClinicalTrials.gov Identifier: NCT04498273.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Factor Xa Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Thrombosis/prevention & control , Adult , Aspirin/adverse effects , COVID-19/complications , Dose-Response Relationship, Drug , Double-Blind Method , Early Termination of Clinical Trials , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Hospitalization , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyridones/administration & dosage , Pyridones/adverse effects
2.
JAMA ; 326(17): 1703-1712, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1460106

ABSTRACT

Importance: Acutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. Objective: To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. Design, Setting, and Participants: The ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m2. Interventions: Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. Results: On June 18, 2021, the trial data and safety monitoring board recommended early termination because of lower than anticipated event rates; at that time, 657 symptomatic outpatients with COVID-19 had been randomized (median age, 54 years [IQR, 46-59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar. Conclusions and Relevance: Among symptomatic clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome. However, the study was terminated after enrollment of 9% of participants because of an event rate lower than anticipated. Trial Registration: ClinicalTrials.gov Identifier: NCT04498273.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Factor Xa Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Thrombosis/prevention & control , Adult , Aspirin/adverse effects , COVID-19/complications , Dose-Response Relationship, Drug , Double-Blind Method , Early Termination of Clinical Trials , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Hospitalization , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyridones/administration & dosage , Pyridones/adverse effects
3.
Cells ; 10(6)2021 06 17.
Article in English | MEDLINE | ID: covidwho-1369745

ABSTRACT

Hypertension is associated with gut bacterial dysbiosis and gut pathology in animal models and people. Butyrate-producing gut bacteria are decreased in hypertension. RNA-seq analysis of gut colonic organoids prepared from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats was used to test the hypothesis that impaired interactions between the gut microbiome and gut epithelium are involved and that these would be remediated with butyrate supplementation. Gene expressions in immune responses including antigen presentation and antiviral pathways were decreased in the gut epithelium of the SHR in organoids and confirmed in vivo; these deficits were corrected by butyrate supplementation. Deficits in gene expression driving epithelial proliferation and differentiation were also observed in SHR. These findings highlight the importance of aligned interactions of the gut microbiome and gut immune responses to blood pressure homeostasis.


Subject(s)
Colon/microbiology , Dysbiosis , Gastrointestinal Microbiome/physiology , Hypertension/microbiology , Animals , Butyrates/pharmacology , Colon/drug effects , Gastrointestinal Microbiome/drug effects , Male , Organoids , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Transcriptome
4.
Contemp Clin Trials ; 109: 106525, 2021 10.
Article in English | MEDLINE | ID: covidwho-1347516

ABSTRACT

BACKGROUND: The SARS CoV-2 virus has caused one of the deadliest pandemics in recent history, resulting in over 170 million deaths and global economic disruption. There remains an urgent need for clinical trials to test therapies for treatment and prevention. DESIGN: An online research platform was created to support a registry community of healthcare workers (HCWs) to understand their experiences and conduct clinical studies to address their concerns. The first study, HERO-HCQ, was a double-blind, multicenter, randomized, pragmatic trial to evaluate the superiority of hydroxychloroquine (HCQ) vs placebo for pre-exposure prophylaxis (PrEP) of COVID-19 clinical infection in HCWs. Secondary objectives were to assess the efficacy of HCQ in preventing viral shedding of COVID-19 among HCWs and to assess the safety and tolerability of HCQ. METHODS: HCWs joined the Registry and were pre-screened for trial interest and eligibility. Trial participants were randomized 1:1 to receive HCQ or placebo. On-site baseline assessment included a COVID-19 nasopharyngeal PCR and blood serology test. Weekly follow-up was done via an online portal and included screening for symptoms of COVID-19, self-reported testing, adverse events, and quality of life assessments. The on-site visit was repeated at Day 30. DISCUSSION: The HERO research platform offers an approach to rapidly engage, screen, invite and enroll into clinical studies using a novel participant-facing online portal interface and remote data collection, enabling limited onsite procedures for conduct of a pragmatic clinical trial. This platform may be an example for future clinical trials of common conditions to enable more rapid evidence generation.


Subject(s)
COVID-19 , Quality of Life , Health Personnel , Humans , SARS-CoV-2 , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL