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Post-exposure Prophylaxis / Preemptive Therapy for SARS-Coronavirus-2 (COVID-19 PEP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04308668
Recruitment Status : Completed
First Posted : March 16, 2020
Results First Posted : May 13, 2021
Last Update Posted : May 13, 2021
Sponsor:
Collaborators:
McGill University Health Centre/Research Institute of the McGill University Health Centre
University of Manitoba
University of Alberta
Information provided by (Responsible Party):
University of Minnesota

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Corona Virus Infection
Acute Respiratory Distress Syndrome
SARS-CoV Infection
Coronavirus
Coronavirus Infections
Interventions Drug: Hydroxychloroquine
Other: Placebo
Enrollment 1312
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment Placebo
Hide Arm/Group Description

Participants in this arm will receive the study drug.

Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days

Participants in this arm will receive a placebo treatment.

Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Period Title: Overall Study
Started 658 654
Completed 622 612
Not Completed 36 42
Reason Not Completed
Lost to Follow-up             32             38
Withdrawal by Subject             4             4
Arm/Group Title Treatment Placebo Total
Hide Arm/Group Description

Participants in this arm will receive the study drug.

Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days

Participants in this arm will receive a placebo treatment.

Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Total of all reporting groups
Overall Number of Baseline Participants 658 654 1312
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 658 participants 654 participants 1312 participants
42  (12) 42  (12) 42  (12)
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Sex Number Analyzed 654 participants 650 participants 1304 participants
Female
354
  54.1%
336
  51.7%
690
  52.9%
Male
300
  45.9%
314
  48.3%
614
  47.1%
Non-binary Number Analyzed 4 participants 4 participants 8 participants
Female
2
  50.0%
2
  50.0%
4
  50.0%
Male
2
  50.0%
2
  50.0%
4
  50.0%
[1]
Measure Analysis Population Description: While biological sex at birth was the question, 4 persons in each arm did not identify as male or female.
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
American Indian or Alaska Native Number Analyzed 658 participants 654 participants 1312 participants
4
   0.6%
2
   0.3%
6
   0.5%
Asian/South Asian Number Analyzed 658 participants 654 participants 1312 participants
204
  31.0%
206
  31.5%
410
  31.3%
Native Hawaiian or Pacific Islander Number Analyzed 658 participants 654 participants 1312 participants
5
   0.8%
4
   0.6%
9
   0.7%
Black or African American Number Analyzed 658 participants 654 participants 1312 participants
28
   4.3%
24
   3.7%
52
   4.0%
White Number Analyzed 658 participants 654 participants 1312 participants
363
  55.2%
379
  58.0%
742
  56.6%
Hispanic or Latino Number Analyzed 658 participants 654 participants 1312 participants
37
   5.6%
36
   5.5%
73
   5.6%
Middle Eastern Number Analyzed 658 participants 654 participants 1312 participants
14
   2.1%
9
   1.4%
23
   1.8%
Unknown/Not Reported Number Analyzed 658 participants 654 participants 1312 participants
12
   1.8%
10
   1.5%
22
   1.7%
[1]
Measure Description: Participants could identify as more than one Race/Ethnicity
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Canada Number Analyzed 658 participants 654 participants 1312 participants
30
   4.6%
29
   4.4%
59
   4.5%
United States Number Analyzed 658 participants 654 participants 1312 participants
628
  95.4%
625
  95.6%
1253
  95.5%
1.Primary Outcome
Title Number of Participants With Active COVID-19 Disease at Day 14 Among Those Who Were Asymptomatic at Baseline
Hide Description Number of participants at 14 days post enrollment with active COVID19 disease among those who were asymptomatic at baseline.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Placebo
Hide Arm/Group Description:

Participants in this arm will receive the study drug.

Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days

Participants in this arm will receive a placebo treatment.

Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Overall Number of Participants Analyzed 414 407
Measure Type: Count of Participants
Unit of Measure: Participants
49
  11.8%
58
  14.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.35
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-7.0 to 2.2
Estimation Comments Values represent percentages. Experimental treatment arm compared with the placebo control arm.
2.Primary Outcome
Title Change in Disease Severity Over 14 Days Among Those Who Are Symptomatic at Baseline
Hide Description Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Time Frame baseline and 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Placebo
Hide Arm/Group Description:

Participants in this arm will receive the study drug.

Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days

Participants in this arm will receive a placebo treatment.

Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Overall Number of Participants Analyzed 212 211
Mean (Standard Error)
Unit of Measure: score on a scale
-2.6  (.12) -2.33  (.12)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.117
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-0.61 to 0.27
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Rate of Hospitalization
Hide Description Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Placebo
Hide Arm/Group Description:

Participants in this arm will receive the study drug.

Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days

Participants in this arm will receive a placebo treatment.

Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Overall Number of Participants Analyzed 645 641
Measure Type: Count of Participants
Unit of Measure: Participants
5
   0.8%
9
   1.4%
4.Secondary Outcome
Title Rate of Death
Hide Description Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease through study completion of 14 days. For those hospitalized within the 14-day study period, the protocol specified follow up would occur for up to 90 days to capture the final outcome of participants' hospitalization. Approximately 30-days was the maximal follow up for hospitalization outcome needed in the trial.
Time Frame Approximately 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Placebo
Hide Arm/Group Description:

Participants in this arm will receive the study drug.

Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days

Participants in this arm will receive a placebo treatment.

Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Overall Number of Participants Analyzed 645 641
Measure Type: Count of Participants
Unit of Measure: Participants
1
   0.2%
1
   0.2%
5.Secondary Outcome
Title Rate of Confirmed SARS-CoV-2 Detection
Hide Description Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Placebo
Hide Arm/Group Description:

Participants in this arm will receive the study drug.

Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days

Participants in this arm will receive a placebo treatment.

Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Overall Number of Participants Analyzed 414 407
Measure Type: Count of Participants
Unit of Measure: Participants
11
   2.7%
9
   2.2%
6.Secondary Outcome
Title Occurrence of Symptoms Compatible With COVID-19 (Possible Disease)
Hide Description Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID-19 infection.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Placebo
Hide Arm/Group Description:

Participants in this arm will receive the study drug.

Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days

Participants in this arm will receive a placebo treatment.

Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Overall Number of Participants Analyzed 414 407
Measure Type: Count of Participants
Unit of Measure: Participants
48
  11.6%
55
  13.5%
7.Secondary Outcome
Title Rate of All-Cause Study Medicine Discontinuation or Withdrawal
Hide Description Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Placebo
Hide Arm/Group Description:

Participants in this arm will receive the study drug.

Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days

Participants in this arm will receive a placebo treatment.

Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Overall Number of Participants Analyzed 645 641
Measure Type: Count of Participants
Unit of Measure: Participants
97
  15.0%
63
   9.8%
8.Secondary Outcome
Title Overall Symptom Severity at 5 and 14 Days
Hide Description Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Time Frame 5 and 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
Early preemptive treatment trial (n=423 symptomatic participants with data)
Arm/Group Title Treatment Placebo
Hide Arm/Group Description:

Participants in this arm will receive the study drug.

Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days

Participants in this arm will receive a placebo treatment.

Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Overall Number of Participants Analyzed 212 211
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
Day 5
-2.22
(-2.53 to -1.9)
-2.05
(-2.37 to -1.73)
Day 14
-3.36
(-3.62 to -3.09)
-3.08
(-3.35 to -2.81)
9.Secondary Outcome
Title Number of Participants With Severe COVID-19 Disease at 14 Days Among Those Who Are Symptomatic at Trial Entry
Hide Description Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the number of participants who report a score of 3.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment Placebo
Hide Arm/Group Description:

Participants in this arm will receive the study drug.

Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days

Participants in this arm will receive a placebo treatment.

Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Overall Number of Participants Analyzed 231 234
Measure Type: Count of Participants
Unit of Measure: Participants
5
   2.2%
8
   3.4%
Time Frame Approximately 30-days
Adverse Event Reporting Description Reporting period was for onset of adverse events within 14 days. All hospitalizations were followed for up to 90 days for final resolution of outcome. Approximately 30 days was the maximal duration needed to capture final outcome.
 
Arm/Group Title Treatment Placebo
Hide Arm/Group Description

Participants in this arm will receive the study drug.

Hydroxychloroquine: 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days

Participants in this arm will receive a placebo treatment.

Placebo: 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

All-Cause Mortality
Treatment Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/658 (0.15%)      1/654 (0.15%)    
Hide Serious Adverse Events
Treatment Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/658 (0.91%)      11/654 (1.68%)    
Cardiac disorders     
Hospitalizations not related to COVID or study medicine  [1]  0/658 (0.00%)  0 2/654 (0.31%)  2
Infections and infestations     
COVID-related hospitalization  [2]  6/658 (0.91%)  6 9/654 (1.38%)  9
Indicates events were collected by systematic assessment
[1]
Adjudication was conducted by blinded investigators.
[2]
n=5 vs. n=8 hospitalizations in early treatment population, n=1 vs. n=1 hospitalizations in postexposure prophylaxis population
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   367/658 (55.78%)      148/654 (22.63%)    
Ear and labyrinth disorders     
Tinnitus   16/658 (2.43%)  16 8/654 (1.22%)  8
Eye disorders     
Visual changes   7/658 (1.06%)  7 5/654 (0.76%)  5
Gastrointestinal disorders     
Nausea or upset stomach   146/658 (22.19%)  146 53/654 (8.10%)  53
Diarrhea, abdominal pain, vomiting   131/658 (19.91%)  131 35/654 (5.35%)  35
General disorders     
Irritability, dizziness, vertigo   39/658 (5.93%)  39 26/654 (3.98%)  26
Headache   15/658 (2.28%)  15 8/654 (1.22%)  8
Taste change or dry mouth   3/658 (0.46%)  3 3/654 (0.46%)  3
Hot flashes, night sweats, palpitations   2/658 (0.30%)  2 1/654 (0.15%)  1
Fatigue   1/658 (0.15%)  1 1/654 (0.15%)  1
Other   1/658 (0.15%)  1 2/654 (0.31%)  2
Immune system disorders     
Allergic reaction (non-anaphylaxis)   6/658 (0.91%)  6 1/654 (0.15%)  1
Psychiatric disorders     
Panic   0/658 (0.00%)  0 1/654 (0.15%)  1
Skin and subcutaneous tissue disorders     
Skin reaction   10/658 (1.52%)  10 4/654 (0.61%)  4
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: David Boulware, MD, MPH
Organization: University of Minnesota
Phone: 6125552020
EMail: covid19@umn.edu
Publications of Results:
Other Publications:
Layout table for additonal information
Responsible Party: University of Minnesota
ClinicalTrials.gov Identifier: NCT04308668    
Other Study ID Numbers: MED-2020-28673
First Submitted: March 11, 2020
First Posted: March 16, 2020
Results First Submitted: April 26, 2021
Results First Posted: May 13, 2021
Last Update Posted: May 13, 2021