Trial Outcomes & Findings for University of Utah COVID-19 Hydrochloroquine Trial (NCT NCT04342169)

NCT ID: NCT04342169

Last Updated: 2023-02-15

Results Overview

Duration of viral shedding, as defined by time from randomization to the first of two consecutive negative swabs, measured on days 1 - 14.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 368 participants
• Primary outcome timeframe: Days
• Results posted on: 2023-02-15

Participant Flow

Enrollment in this trial is synonymous with treatment assignment/randomization.

Participant milestones

Measure	Hydroxychloroquine Participants randomized to the HCQ arm will receive HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days. The drug dose (2.4 gm over 5 days) falls at the lower end of doses proposed in various international trials, but it has proven in vitro efficacy, with a ratio of lung tissue trough concentrations to the EC50 (effective concentration to suppress 50% of viral activity) of \>20. Hydroxychloroquine: HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days	Placebo Those randomized to placebo will receive a placebo to be taken on the same schedule. Placebo oral tablet: Placebo to be taken on the same schedule as HCQ.
Overall Study STARTED	185	183
Overall Study COMPLETED	89	89
Overall Study NOT COMPLETED	96	94

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

University of Utah COVID-19 Hydrochloroquine Trial

Baseline characteristics by cohort

Measure	Hydroxychloroquine n=185 Participants Participants randomized to the HCQ arm will receive HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days. The drug dose (2.4 gm over 5 days) falls at the lower end of doses proposed in various international trials, but it has proven in vitro efficacy, with a ratio of lung tissue trough concentrations to the EC50 (effective concentration to suppress 50% of viral activity) of \>20. Hydroxychloroquine: HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days	Placebo n=182 Participants Those randomized to placebo will receive a placebo to be taken on the same schedule. Placebo oral tablet: Placebo to be taken on the same schedule as HCQ.	Total n=367 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	165 Participants n=5 Participants	164 Participants n=7 Participants	329 Participants n=5 Participants
Age, Categorical >=65 years	19 Participants n=5 Participants	17 Participants n=7 Participants	36 Participants n=5 Participants
Age, Continuous	42.1 years STANDARD_DEVIATION 14.70 • n=5 Participants	41.8 years STANDARD_DEVIATION 14.40 • n=7 Participants	41.9 years STANDARD_DEVIATION 14.53 • n=5 Participants
Sex: Female, Male Female	90 Participants n=5 Participants	86 Participants n=7 Participants	176 Participants n=5 Participants
Sex: Female, Male Male	95 Participants n=5 Participants	96 Participants n=7 Participants	191 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	79 Participants n=5 Participants	79 Participants n=7 Participants	158 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	84 Participants n=5 Participants	87 Participants n=7 Participants	171 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	22 Participants n=5 Participants	16 Participants n=7 Participants	38 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	86 Participants n=5 Participants	80 Participants n=7 Participants	166 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	96 Participants n=5 Participants	96 Participants n=7 Participants	192 Participants n=5 Participants
Region of Enrollment United States	185 participants n=5 Participants	182 participants n=7 Participants	367 participants n=5 Participants

PRIMARY outcome

Timeframe: Days

Population: Those randomized with swabs collected

Duration of viral shedding, as defined by time from randomization to the first of two consecutive negative swabs, measured on days 1 - 14.

Outcome measures

Measure	Hydroxychloroquine n=158 Participants Participants randomized to the HCQ arm will receive HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days. The drug dose (2.4 gm over 5 days) falls at the lower end of doses proposed in various international trials, but it has proven in vitro efficacy, with a ratio of lung tissue trough concentrations to the EC50 (effective concentration to suppress 50% of viral activity) of \>20. Hydroxychloroquine: HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days	Placebo n=162 Participants Those randomized to placebo will receive a placebo to be taken on the same schedule. Placebo oral tablet: Placebo to be taken on the same schedule as HCQ.
Duration of Viral Shedding	9.532447 Days Standard Error 0.3707	10.39556 Days Standard Error 0.3466

SECONDARY outcome

Timeframe: Days 1-15

Population: Among ITT that were symptomatic at baseline

Duration of COVID-19 symptoms (through DayA15):

this is an integer-valued outcome which is defined as date of first asymptomatic date through the start date.

To determine the end date, first each symptom assessment from baseline through DayA15, inclusive, will be classified as symptomatic, asymptomatic, or unknown.

A symptomatic day is one in which at least one of the core symptoms is observed to exceed the permissible threshold: not experiencing for fever and chills; extremely mild for shortness of breath, diarrhea, and muscle aches; mild for cough and tiredness. If at most one symptom level is missing on a given day and all observed core symptoms' levels are at or below the permissible threshold, the day will be classified as asymptomatic. Otherwise (i.e. if at most five of the core symptoms have a reported symptom level and none of the reported symptom levels exceeded the threshold), the day will be considered unknown.

Outcome measures

Measure	Hydroxychloroquine n=154 Participants Participants randomized to the HCQ arm will receive HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days. The drug dose (2.4 gm over 5 days) falls at the lower end of doses proposed in various international trials, but it has proven in vitro efficacy, with a ratio of lung tissue trough concentrations to the EC50 (effective concentration to suppress 50% of viral activity) of \>20. Hydroxychloroquine: HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days	Placebo n=154 Participants Those randomized to placebo will receive a placebo to be taken on the same schedule. Placebo oral tablet: Placebo to be taken on the same schedule as HCQ.
Duration of COVID-19-attributable Symptoms	6 Days Interval 3.0 to 13.0	6 Days Interval 3.0 to 10.0

SECONDARY outcome

Timeframe: within 14 days of enrollment

Population: Hospitalization status unknown for 33 (3 Safety) Hydroxychloroquine, and 31 (5 Safety) Placebo participants

Outcome is summarized by treatment received; all other summaries show treatment assigned

Outcome measures

Measure	Hydroxychloroquine n=152 Participants Participants randomized to the HCQ arm will receive HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days. The drug dose (2.4 gm over 5 days) falls at the lower end of doses proposed in various international trials, but it has proven in vitro efficacy, with a ratio of lung tissue trough concentrations to the EC50 (effective concentration to suppress 50% of viral activity) of \>20. Hydroxychloroquine: HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days	Placebo n=151 Participants Those randomized to placebo will receive a placebo to be taken on the same schedule. Placebo oral tablet: Placebo to be taken on the same schedule as HCQ.
Hospitalization	7 Participants	4 Participants

SECONDARY outcome

Timeframe: Day 28

The definition of the persistence of viral shedding on Day 28 outcome relies heavily on the Day 28 swab and is limited to those who have a test result for the Day 28 swab or who are not known to have died on or before DayR + 30 (there is a 2 day window for collecting the Day 28 swab). If the Day 28 swab result is known, the result will be used to define the outcome ("yes" if positive, "no" if negative). Otherwise, subjects with a confirmed cessation of viral shedding when considering daily swab results from DayR + 1 to DayR + 25, inclusive (with the requirement for confirmation waived if the latest available daily result in this interval is negative), and a missing Day 28 value will be assumed to be negative on Day 28; otherwise subjects hospitalized on any of the days DayR + 26{DayR + 30 with a missing Day 28 value will be assumed to be positive on Day 28; otherwise, multiple imputation will be performed.

Outcome measures

Measure	Hydroxychloroquine n=185 Participants Participants randomized to the HCQ arm will receive HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days. The drug dose (2.4 gm over 5 days) falls at the lower end of doses proposed in various international trials, but it has proven in vitro efficacy, with a ratio of lung tissue trough concentrations to the EC50 (effective concentration to suppress 50% of viral activity) of \>20. Hydroxychloroquine: HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days	Placebo n=182 Participants Those randomized to placebo will receive a placebo to be taken on the same schedule. Placebo oral tablet: Placebo to be taken on the same schedule as HCQ.
Number of Participants With Viral Shedding on Day 28	30 Participants	30 Participants

SECONDARY outcome

Timeframe: Days 1-14

Population: Eligible households are those with at least 2 adults, where no other adult besides the index subject is positive for COVID-19 at baseline, and where another adult submitted swab samples.

This outcome will be analyzed for households with at least two adults for which no other adult besides the index study subject is positive for COVID-19 at baseline and for which the index study subject is in the ITT population. This binary outcome will be at the household level and will be a "yes" if there is a positive swab by one or more adult household contacts for any of the study-administered swabs from days DayR + 1 to DayR + 14, inclusive. If there are no positive swabs but at least one negative swab, the outcome will be a "no;" otherwise it will be missing.

Outcome measures

Measure	Hydroxychloroquine n=33 households with at least two adults for Participants randomized to the HCQ arm will receive HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days. The drug dose (2.4 gm over 5 days) falls at the lower end of doses proposed in various international trials, but it has proven in vitro efficacy, with a ratio of lung tissue trough concentrations to the EC50 (effective concentration to suppress 50% of viral activity) of \>20. Hydroxychloroquine: HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days	Placebo n=39 households with at least two adults for Those randomized to placebo will receive a placebo to be taken on the same schedule. Placebo oral tablet: Placebo to be taken on the same schedule as HCQ.
Adult Household Contact Viral Acquisition	16 households with at least two adults for	19 households with at least two adults for

Adverse Events

Hydroxychloroquine

Serious events: 9 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Hydroxychloroquine n=185 participants at risk Participants randomized to the HCQ arm will receive HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days. The drug dose (2.4 gm over 5 days) falls at the lower end of doses proposed in various international trials, but it has proven in vitro efficacy, with a ratio of lung tissue trough concentrations to the EC50 (effective concentration to suppress 50% of viral activity) of \>20. Hydroxychloroquine: HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days	Placebo n=183 participants at risk Those randomized to placebo will receive a placebo to be taken on the same schedule. Placebo oral tablet: Placebo to be taken on the same schedule as HCQ.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/185 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.	0.55% 1/183 • Number of events 1 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.
Surgical and medical procedures Shoulder Arthroplasty	0.00% 0/185 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.	0.55% 1/183 • Number of events 1 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.
Infections and infestations Acute appendicitis	0.00% 0/185 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.	0.55% 1/183 • Number of events 1 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.
Infections and infestations COVID-19 Pneumonia	0.00% 0/185 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.	0.55% 1/183 • Number of events 1 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.
Surgical and medical procedures Hospitalization	0.00% 0/185 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.	0.55% 1/183 • Number of events 1 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.54% 1/185 • Number of events 1 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.	0.55% 1/183 • Number of events 1 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.
Infections and infestations Diabetic Foot Infection	0.54% 1/185 • Number of events 1 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.	0.00% 0/183 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.
Respiratory, thoracic and mediastinal disorders Shortness of breath	0.54% 1/185 • Number of events 1 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.	0.00% 0/183 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.
Gastrointestinal disorders Upper gastrointestinal bleeding	0.54% 1/185 • Number of events 1 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.	0.00% 0/183 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.
Respiratory, thoracic and mediastinal disorders Hypoxic respiratory failure	2.2% 4/185 • Number of events 4 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.	0.00% 0/183 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.
Investigations Oxygen saturation low	0.54% 1/185 • Number of events 1 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.	0.00% 0/183 • Randomization through Day 14 or hospitalization, whichever occurs first. We collected AEs that were 1. serious adverse events, 2. non-serious adverse events that are considered by the investigator to be related to study drug or study procedures or of uncertain relationship, and 3. adverse events that lead to permanent discontinuation of the study drug.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Adam Spivak

University of Utah School of Medicine Division of Infectious Diseases

Phone: 8015871964

Email: adam.spivak@hsc.utah.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place