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.
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.
Drug: Hydroxychloroquine (HCQ)
Administered orally
Drug: Azithromycin (Azithro)
Administered orally
Drug: Placebo for Hydroxychloroquine
Administered orally
Drug: Placebo for Azithromycin
Administered orally
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
- Cough
- Shortness of breath or difficulty breathing at rest or with exertion
- Sore throat
- Body pain or muscle pain
- Fatigue
- Headache
- 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-19.
- 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.
- Loop diuretics are exceptions to above exclusion criterion but these cannot be used
within 30 days prior to study entry.
- Participated in a study where co-enrollment was not allowed.
- Receipt of a SARS-CoV-2 vaccination prior to study entry.
- Known allergy/sensitivity or any hypersensitivity to components of HCQ, azithromycin,
or their formulation.
- More than 10 days of any of the following symptoms attributed to the SARS-CoV-2
infection at study entry:
- Fever (can be subjective) or feeling feverish
- Cough
- Shortness of breath or difficulty breathing at rest or with exertion
- Sore throat
- Body pain or muscle pain
- Fatigue
- Headache
- Chills
- Nasal obstruction or congestion
- Loss of taste or smell
- Nausea or vomiting
- Diarrhea
Alabama CRS
Birmingham, Alabama, United States
UCSD Antiviral Research Center CRS
San Diego, California, United States
Harbor-UCLA CRS
Torrance, California, United States
Whitman-Walker Health CRS
Washington, District of Columbia, United States
Northwestern University CRS
Chicago, Illinois, United States
Rush University CRS
Chicago, Illinois, United States
Greensboro CRS
Greensboro, North Carolina, United States
Cincinnati Clinical Research Site
Cincinnati, Ohio, United States
University of Pittsburgh CRS
Pittsburgh, Pennsylvania, United States
Trinity Health and Wellness Center CRS
Dallas, Texas, United States
University of Washington AIDS CRS
Seattle, Washington, United States
Davey Smith, MD, Study Chair
University of California, San Diego