Trial Outcomes & Findings for Hydroxychloroquine Monotherapy and in Combination With Azithromycin in Patients With Moderate and Severe COVID-19 Disease (NCT NCT04358081)

Last Updated: 2021-10-11

Results Overview

Clinical response was defined as a) discharged alive; or b) No need for mechanical ventilation in any participants and no need for supplemental oxygen requirement (SpO2) in participants without pre-morbid O2 requirement.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

20 participants

Primary outcome timeframe

15 days

Results posted on

2021-10-11

Participant Flow

Study was conducted in 9 centers in the United States. A total of 20 participants were randomized, of whom 19 were treated.

One patient was mis-randomized and never received any treatment. This patient has creatine clearance level \<45 mL/min or required acute renal replacement therapy and therefore was not eligible for inclusion in the study.

Participant milestones

Participant milestones
Measure	Arm 1: Hydroxychloroquine + Aithromycin Placebo Hydroxychloroquine 600mg o.d. as loading dose (Day 1) +followed by 200mg t.i.d was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin placebo o.d.	Arm 2: Hydroxychloroquine + Azithromycin Hydroxychloroquine 600 mg o.d. as a loading dose (Day 1) followed by 200 mg t.i.d. was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin: 500 mg as a loading dose (Day 1) followed by 250 mg o.d. Day 2 - Day 5	Arm 3: Hydroxychloroquine Placebo + Azithromycin Placebo Hydroxychloroquine placebo o.d. (day 1) followed by hydroxychloroquine placebo t.i.d Azythromycin placebo o.d.
Treatment Phase of Study STARTED	7	7	5
Treatment Phase of Study COMPLETED	3	6	2
Treatment Phase of Study NOT COMPLETED	4	1	3
Study Completion Phase STARTED	7	7	5
Study Completion Phase COMPLETED	6	7	3
Study Completion Phase NOT COMPLETED	1	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1: Hydroxychloroquine + Aithromycin Placebo Hydroxychloroquine 600mg o.d. as loading dose (Day 1) +followed by 200mg t.i.d was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin placebo o.d.	Arm 2: Hydroxychloroquine + Azithromycin Hydroxychloroquine 600 mg o.d. as a loading dose (Day 1) followed by 200 mg t.i.d. was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin: 500 mg as a loading dose (Day 1) followed by 250 mg o.d. Day 2 - Day 5	Arm 3: Hydroxychloroquine Placebo + Azithromycin Placebo Hydroxychloroquine placebo o.d. (day 1) followed by hydroxychloroquine placebo t.i.d Azythromycin placebo o.d.
Treatment Phase of Study Withdrawal by Subject	0	1	1
Treatment Phase of Study Adverse Event	1	0	1
Treatment Phase of Study Physician Decision	2	0	1
Treatment Phase of Study Protocol Violation	1	0	0
Study Completion Phase Death	0	0	1
Study Completion Phase Lost to Follow-up	1	0	1

Baseline Characteristics

FAS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: Hydroxychloroquine + Aithromycin Placebo n=7 Participants Hydroxychloroquine 600mg o.d. as loading dose (Day 1) +followed by 200mg t.i.d was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin placebo o.d.	Arm 2: Hydroxychloroquine + Azithromycin n=7 Participants Hydroxychloroquine 600 mg o.d. as a loading dose (Day 1) followed by 200 mg t.i.d. was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin: 500 mg as a loading dose (Day 1) followed by 250 mg o.d. Day 2 - Day 5	Arm 3: Hydroxychloroquine Placebo + Azithromycin Placebo n=5 Participants Hydroxychloroquine placebo o.d. (day 1) followed by hydroxychloroquine placebo t.i.d Azythromycin placebo o.d.	Total n=19 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	16 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Age, Continuous	45.9 years STANDARD_DEVIATION 10.6 • n=5 Participants	60.9 years STANDARD_DEVIATION 12.5 • n=7 Participants	55.2 years STANDARD_DEVIATION 11.1 • n=5 Participants	53.8 years STANDARD_DEVIATION 12.7 • n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	12 Participants n=4 Participants
Race/Ethnicity, Customized White	1 Participants n=5 Participants • FAS	3 Participants n=7 Participants • FAS	3 Participants n=5 Participants • FAS	7 Participants n=4 Participants • FAS
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants • FAS	1 Participants n=7 Participants • FAS	0 Participants n=5 Participants • FAS	3 Participants n=4 Participants • FAS
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants • FAS	0 Participants n=7 Participants • FAS	0 Participants n=5 Participants • FAS	1 Participants n=4 Participants • FAS
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants • FAS	0 Participants n=7 Participants • FAS	0 Participants n=5 Participants • FAS	1 Participants n=4 Participants • FAS
Race/Ethnicity, Customized Unknown	2 Participants n=5 Participants • FAS	3 Participants n=7 Participants • FAS	2 Participants n=5 Participants • FAS	7 Participants n=4 Participants • FAS

PRIMARY outcome

Timeframe: 15 days

Population: Full Analysis Set (FAS) was comprised of all participants to whom study treatment had been assigned by randomization excluding one mis-randomized participant.

Outcome measures

Outcome measures
Measure	Arm 1: Hydroxychloroquine + Aithromycin Placebo n=7 Participants Hydroxychloroquine 600mg o.d. as loading dose (Day 1) +followed by 200mg t.i.d was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin placebo o.d.	Arm 2: Hydroxychloroquine + Azithromycin n=7 Participants Hydroxychloroquine 600 mg o.d. as a loading dose (Day 1) followed by 200 mg t.i.d. was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin: 500 mg as a loading dose (Day 1) followed by 250 mg o.d. Day 2 - Day 5	Arm 3: Hydroxychloroquine Placebo + Azithromycin Placebo n=5 Participants Hydroxychloroquine placebo o.d. (day 1) followed by hydroxychloroquine placebo t.i.d Azythromycin placebo o.d.
Number of Participants Who Achieved Clinical Response by Day 15	7 Participants	7 Participants	4 Participants

SECONDARY outcome

Timeframe: 6 days and 10 Days

Population: FAS

Number and percentage of participants with negative or below LLOQ SARS-COV-2 based on polymerase chain reaction (PCR) test

Outcome measures

Outcome measures
Measure	Arm 1: Hydroxychloroquine + Aithromycin Placebo n=7 Participants Hydroxychloroquine 600mg o.d. as loading dose (Day 1) +followed by 200mg t.i.d was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin placebo o.d.	Arm 2: Hydroxychloroquine + Azithromycin n=7 Participants Hydroxychloroquine 600 mg o.d. as a loading dose (Day 1) followed by 200 mg t.i.d. was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin: 500 mg as a loading dose (Day 1) followed by 250 mg o.d. Day 2 - Day 5	Arm 3: Hydroxychloroquine Placebo + Azithromycin Placebo n=5 Participants Hydroxychloroquine placebo o.d. (day 1) followed by hydroxychloroquine placebo t.i.d Azythromycin placebo o.d.
Number of Participants Who Achieved Viral Clearance by 6 days	2 Participants	3 Participants	3 Participants
Number of Participants Who Achieved Viral Clearance by 10 days	2 Participants	3 Participants	3 Participants

SECONDARY outcome

Timeframe: 15 days

Population: FAS

Number of participants who received hydrochloroquine plus azithromycin relative to placebo who were discharged from hospital

Outcome measures

Outcome measures
Measure	Arm 1: Hydroxychloroquine + Aithromycin Placebo n=7 Participants Hydroxychloroquine 600mg o.d. as loading dose (Day 1) +followed by 200mg t.i.d was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin placebo o.d.	Arm 2: Hydroxychloroquine + Azithromycin n=7 Participants Hydroxychloroquine 600 mg o.d. as a loading dose (Day 1) followed by 200 mg t.i.d. was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin: 500 mg as a loading dose (Day 1) followed by 250 mg o.d. Day 2 - Day 5	Arm 3: Hydroxychloroquine Placebo + Azithromycin Placebo n=5 Participants Hydroxychloroquine placebo o.d. (day 1) followed by hydroxychloroquine placebo t.i.d Azythromycin placebo o.d.
Number of Participants Discharged or Ready for Discharge	7 participants	7 participants	4 participants

SECONDARY outcome

Timeframe: 15 days

Population: FAS

Number of participants requiring supplemental oxygen at the time of randomization who returned to pre-morbid supplemental oxygen

Outcome measures

Outcome measures
Measure	Arm 1: Hydroxychloroquine + Aithromycin Placebo n=7 Participants Hydroxychloroquine 600mg o.d. as loading dose (Day 1) +followed by 200mg t.i.d was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin placebo o.d.	Arm 2: Hydroxychloroquine + Azithromycin n=7 Participants Hydroxychloroquine 600 mg o.d. as a loading dose (Day 1) followed by 200 mg t.i.d. was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin: 500 mg as a loading dose (Day 1) followed by 250 mg o.d. Day 2 - Day 5	Arm 3: Hydroxychloroquine Placebo + Azithromycin Placebo n=5 Participants Hydroxychloroquine placebo o.d. (day 1) followed by hydroxychloroquine placebo t.i.d Azythromycin placebo o.d.
Time to Return to Pre-morbid Supplemental Oxygen Requirement in Participants Receiving Hydrochloroquine or Hydrochloroquine Plus Azithromycin Relative to Placebo	7 participants	6 participants	4 participants

Adverse Events

Hydroxychloroquine + Aithromycin Placebo

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Hydroxychloroquine + Azithromycin

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Hydroxychloroquine Placebo + Azithromycin Placebo

Serious events: 2 serious events

Other events: 2 other events

Deaths: 1 deaths

Total

Serious events: 3 serious events

Other events: 11 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Hydroxychloroquine + Aithromycin Placebo n=7 participants at risk HCQ	Hydroxychloroquine + Azithromycin n=7 participants at risk HCQ + AZI	Hydroxychloroquine Placebo + Azithromycin Placebo n=5 participants at risk HCG + AZI + Placebo	Total n=19 participants at risk Total
Cardiac disorders Cardiac arrest	0.00% 0/7 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days	0.00% 0/7 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days	20.0% 1/5 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days	5.3% 1/19 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days
Renal and urinary disorders Acute kidney injury	0.00% 0/7 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days	0.00% 0/7 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days	20.0% 1/5 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days	5.3% 1/19 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days
Respiratory, thoracic and mediastinal disorders Hypoxia	14.3% 1/7 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days	0.00% 0/7 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days	0.00% 0/5 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days	5.3% 1/19 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days
Respiratory, thoracic and mediastinal disorders Tachypnoea	0.00% 0/7 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days	0.00% 0/7 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days	20.0% 1/5 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days	5.3% 1/19 • at day 15 Adverse Events (AEs) are any untoward sign or symptom that occured during the study treatment period of 15 days

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: +1 (862) 778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER