Clinical trial NCT04341727: Hydroxychloroquine,Hydroxychloroquine,Azithromycin in the Treatment of SARS CoV-2 Infection
Official title: Open-label, Randomized Controlled Trial of Hydroxychloroquine, Hydroxychloroquine Plus Azithromycin, Chloroquine Alone, Chloroquine Plus Azithromycin in the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) Infection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Coronavirus Infection
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2020-04-10
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This Phase III trial four treatment strategies non-critically ill hospitalized participants (not requiring intensive care unit (ICU) admission and/or mechanical ventilation) with SARS CoV-2 infection, Participants will receive hydroxychloroquine or chloroquine with or without azithromycin.

Detailed description: This Phase III trial will utilize four treatment strategies in non-critically ill hospitalized participants (not requiring mechanical ventilation) with SARS CoV-2 infection, Participants will receive hydroxychloroquine or chloroquine with or without azithromycin. Investigators are primarily interested in the time to recovery. In addition to study medications there will be daily symptom surveys for 14 days, then weekly thereafter for 4 weeks resulting in a total duration of follow up of 42 days. During hospitalization, daily symptom surveys will be completed in conjunction with the study coordinators. On discharge participants will have the option to complete electronic symptom surveys or complete symptom surveys via telephone with study coordinator. In the event that the participant opts for electronic symptom surveys on discharge participants will in addition receive a follow up call from a study coordination every 7 days during the initial 14 day period. In addition, failure to submit a symptom survey will prompt a study follow up call. Data from standard of care SOC will be collected from medical records.

Eligibility criteria: Inclusion Criteria:

* Hospitalization for management of SARS CoV-2 infection
* Positive SARS CoV-2 test
* Age \>=18 years
* Provision of informed consent
* Electrocardiogram (ECG) ≤48 hours prior to enrollment
* Complete blood count, glucose-6 phosphate-dehydrogenase (G6PD), comprehensive metabolic panel and magnesium ≤48 hours prior to enrollment from standard of care.
* If participating in sexual activity that could lead to pregnancy, individuals of reproductive potential who can become pregnant must agree to use contraception throughout the study. At least one of the following must be used throughout the study:

  * Condom (male or female) with or without spermicide
  * Diaphragm or cervical cap with spermicide
  * Intrauterine device (IUD)
  * Hormone-based contraceptive

Exclusion Criteria:

* Contraindication or allergy to chloroquine, hydroxychloroquine or azithromycin
* Current use hydroxychloroquine, chloroquine or azithromycin
* Concurrent use of another investigational agent
* Invasive mechanical ventilation
* Participants who have any severe and/or uncontrolled medical conditions such as:

  * unstable angina pectoris,
  * symptomatic congestive heart failure,
  * myocardial infarction,
  * cardiac arrhythmias or know prolonged QTc \>470 males, \>480 female on ECG
  * pulmonary insufficiency,
  * epilepsy (interaction with chloroquine),
* Prior retinal eye disease
* Concurrent malignancy requiring chemotherapy
* Known Chronic Kidney disease, eGFR\<10 or dialysis
* G-6-PD deficiency, if unknown requires G6PD testing prior to enrollment

  * Known Porphyria
  * Known myasthenia gravis
  * Currently pregnant or planning on getting pregnant while on study
  * Breast feeding
  * AST/ALT \>five times the upper limit of normal ULN\*
  * Bilirubin \>five times the ULN\*
  * Magnesium \<1.4 mEq/L\*
  * Calcium \<8.4mg/dL \>10.6mg/dL\*
  * Potassium \<3.3 \>5.5 mEg/L\*

Primary outcomes:
measure: Hours to Recovery
timeFrame: 42 days
Secondary outcomes:
measure: Time to Fever Resolution
timeFrame: 42 days
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine Infectious Disease Clinical Research Unit
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine (ID-CRU)
name: Jane O'Halloran, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: