A Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy of Hydroxychloroquine and Azithromycin to Prevent Hospitalization or Death in Persons With COVID-19
Overview
- Phase
- Phase 2
- Intervention
- Hydroxychloroquine (HCQ)
- Conditions
- COVID-19
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 20
- Locations
- 11
- Primary Endpoint
- Number of Participants Who Died From Any Cause or Were Hospitalized
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study was to evaluate the efficacy of hydroxychloroquine (HCQ) and azithromycin (Azithro) to prevent hospitalization or death in symptomatic adult outpatients with COVID-19 caused by SARS-CoV-2 infection.
Detailed Description
This Phase IIB study was designed to evaluate the efficacy of hydroxychloroquine (HCQ) and azithromycin (Azithro) to prevent hospitalization or death in symptomatic adult outpatients with COVID-19 caused by SARS-CoV-2 infection. Participants were randomized 1:1 to receive active or placebo study treatment. The target sample size was 2000 participants, with approximately 1000 in each arm. Stratification was by "high" versus "low" risk of progression to severe COVID-19, where "high risk" was defined as a person age ≥60 years or having at least one of several specified comorbidities. Participants were prescribed study treatment for 7 days and were to be followed for an additional 24 weeks. Assessments on a subset of participants were planned to include blood collection, self-collected nasal swabs, and nasopharyngeal swabs. On June 23, 2020, sites were informed that the study was closing to follow-up due to slow enrollment and lack of community enthusiasm. Follow-up through week 24 was not completed for any participant. Participants were asked to complete the Day 20 visit and then were discontinued from the study. Due to the early termination, enrollment into the specimen collection subset did not occur, and results associated with those specimens are not available. Due to the small number of participants enrolled, some statistical tests were not able to be performed and only descriptive results are provided.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Documentation of confirmed active severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection from any respiratory specimen collected ≤7 days from when the first dose of study treatment was expected to be taken.
- •Experienced at least one of the following SARS-CoV-2 infection symptoms within 24 hours of screening (symptom(s) must be new or worse compared to pre-COVID-19 health status):
- •Fever (can be subjective) or feeling feverish
- •Shortness of breath or difficulty breathing at rest or with exertion
- •Sore throat
- •Body pain or muscle pain
- •Agreed to not participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 during the study period up until reaching hospitalization or 20 days, whichever is earliest.
- •Agreed to not obtain study medications outside of the A5395 study.
Exclusion Criteria
- •Need for hospitalization or immediate medical attention in the clinical opinion of the study investigator.
- •History of or current hospitalization for COVID-
- •History of ventricular arrhythmia or use of antiarrhythmics within 30 days prior to entry.
- •Personal or family history of Long QT syndrome.
- •History of kidney disease.
- •History of ischemic or structural heart disease.
- •History of hypokalemia or hypomagnesemia or taking potassium supplementation or magnesium supplementation
- •Personal medical history of porphyria, retinopathy, severe hepatic impairment, or glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- •Used drugs with possible anti-SARS-CoV-2 activity within 30 days prior to study entry, e.g., remdesivir, lopinavir/ritonavir fixed dose combination, ribavirin, chloroquine, hydroxychloroquine, and azithromycin, or participation in a clinical trial involving any of these drugs whether for treatment or prophylaxis.
- •Requirement or expected requirement for a medication that significantly prolongs QT intervals or increases risk for QT prolongation.
Arms & Interventions
Arm A: Hydroxychloroquine (HCQ) and Azithromycin (Azithro)
Hydroxychloroquine 400 mg (administered as two 200 mg capsules) orally twice daily for 2 doses starting on Day 0, followed by 200 mg (administered as one 200 mg capsule) orally twice daily for 12 doses (6 days), PLUS: Azithromycin 500 mg (administered as two 250 mg capsules) orally as a single dose on Day 0, followed by 250 mg (administered as one 250 mg capsule) orally once daily for 4 doses (4 days).
Intervention: Hydroxychloroquine (HCQ)
Arm A: Hydroxychloroquine (HCQ) and Azithromycin (Azithro)
Hydroxychloroquine 400 mg (administered as two 200 mg capsules) orally twice daily for 2 doses starting on Day 0, followed by 200 mg (administered as one 200 mg capsule) orally twice daily for 12 doses (6 days), PLUS: Azithromycin 500 mg (administered as two 250 mg capsules) orally as a single dose on Day 0, followed by 250 mg (administered as one 250 mg capsule) orally once daily for 4 doses (4 days).
Intervention: Azithromycin (Azithro)
Arm B: Placebo for Hydroxychloroquine and Azithromycin
Placebo for Hydroxychloroquine (administered as two matching placebo capsules) orally twice daily for 2 doses starting on Day 0, followed by Placebo for HCQ (administered as one 200 mg capsule) orally twice daily for 12 doses (6 days), PLUS: Placebo for Azithromycin (administered as two matching placebo capsules) orally as a single dose on Day 0, followed by Placebo for Azithromycin (administered as one matching placebo capsule) orally once daily for 4 doses (4 days).
Intervention: Placebo for Hydroxychloroquine
Arm B: Placebo for Hydroxychloroquine and Azithromycin
Placebo for Hydroxychloroquine (administered as two matching placebo capsules) orally twice daily for 2 doses starting on Day 0, followed by Placebo for HCQ (administered as one 200 mg capsule) orally twice daily for 12 doses (6 days), PLUS: Placebo for Azithromycin (administered as two matching placebo capsules) orally as a single dose on Day 0, followed by Placebo for Azithromycin (administered as one matching placebo capsule) orally once daily for 4 doses (4 days).
Intervention: Placebo for Azithromycin
Outcomes
Primary Outcomes
Number of Participants Who Died From Any Cause or Were Hospitalized
Time Frame: The 20-day period from and including the day of the first dose of study treatment
Hospitalization was defined as requiring at least 24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to address needs during the COVID-19 pandemic. Evaluation at a hospital or similar facility with less than 24 hours of acute care was not considered a hospitalization. Formal statistical testing was not conducted due to the small number of participants and events.
Secondary Outcomes
- Number of Participants Who Died From Any Cause(The 20-day period from and including the day of the first dose of study treatment)
- Number of Participants Who Died From Any Cause or Were Hospitalized Through the End of Follow-up(From day of the first dose of study treatment to Week 24)
- Number of Participants Who Died From Any Cause, or Were Hospitalized, or Had an Urgent Visit to Emergency Room or Clinic(The 20-day period from and including the day of the first dose of study treatment)
- Number of Participants Who Prematurely Discontinue Study Treatment Due to an Adverse Event(From start of study treatment through Day 7)
- Number of Participants Who Had Any Cardiac Adverse Events(From start of study treatment through Day 20)
- Participant-specific Area Under the Curve (AUC) of the Symptom Score Associated With COVID-19 Disease Over Time(Day 0 to Day 20, 21 days total)
- Time to Self-reported Return to Usual (Pre-COVID) Health.(Day 0 to Day 20, 21 days total)
- Duration of Fever(Day 0 to Day 20, 21 days total)
- Duration of Symptoms Associated With COVID-19 Disease(Day 0 to Day 20, 21 days total)
- SARS-CoV-2 RNA Detection Status From Self-collected Nasal and Site-collected NP Swabs Among Subset(Measured at entry, Day 6, and Day 20)
- SARS-CoV-2 RNA Level (Continuous) From Self-collected Nasal and Site-collected NP Swabs Among Subset(Measured at entry, Day 6, and Day 20)
- Number of Participants With an Occurrence of Fainting(From start of study treatment through Day 20)