Trial Outcomes & Findings for Post-exposure Prophylaxis / Preemptive Therapy for SARS-Coronavirus-2 (NCT NCT04308668)

NCT ID: NCT04308668

Last Updated: 2021-05-13

Results Overview

Number of participants at 14 days post enrollment with active COVID19 disease among those who were asymptomatic at baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1312 participants
• Primary outcome timeframe: 14 days
• Results posted on: 2021-05-13

Participant Flow

Participant milestones

Measure	Treatment 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	Placebo 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 Study STARTED	658	654
Overall Study COMPLETED	622	612
Overall Study NOT COMPLETED	36	42

Reasons for withdrawal

Measure	Treatment 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	Placebo 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 Study Lost to Follow-up	32	38
Overall Study Withdrawal by Subject	4	4

Baseline Characteristics

While biological sex at birth was the question, 4 persons in each arm did not identify as male or female.

Baseline characteristics by cohort

Measure	Treatment n=658 Participants 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	Placebo n=654 Participants 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 n=1312 Participants Total of all reporting groups
Age, Continuous	42 years STANDARD_DEVIATION 12 • n=658 Participants	42 years STANDARD_DEVIATION 12 • n=654 Participants	42 years STANDARD_DEVIATION 12 • n=1312 Participants
Sex: Female, Male Sex · Female	354 Participants n=654 Participants • While biological sex at birth was the question, 4 persons in each arm did not identify as male or female.	336 Participants n=650 Participants • While biological sex at birth was the question, 4 persons in each arm did not identify as male or female.	690 Participants n=1304 Participants • While biological sex at birth was the question, 4 persons in each arm did not identify as male or female.
Sex: Female, Male Sex · Male	300 Participants n=654 Participants • While biological sex at birth was the question, 4 persons in each arm did not identify as male or female.	314 Participants n=650 Participants • While biological sex at birth was the question, 4 persons in each arm did not identify as male or female.	614 Participants n=1304 Participants • While biological sex at birth was the question, 4 persons in each arm did not identify as male or female.
Sex: Female, Male Non-binary · Female	2 Participants n=4 Participants • While biological sex at birth was the question, 4 persons in each arm did not identify as male or female.	2 Participants n=4 Participants • While biological sex at birth was the question, 4 persons in each arm did not identify as male or female.	4 Participants n=8 Participants • While biological sex at birth was the question, 4 persons in each arm did not identify as male or female.
Sex: Female, Male Non-binary · Male	2 Participants n=4 Participants • While biological sex at birth was the question, 4 persons in each arm did not identify as male or female.	2 Participants n=4 Participants • While biological sex at birth was the question, 4 persons in each arm did not identify as male or female.	4 Participants n=8 Participants • While biological sex at birth was the question, 4 persons in each arm did not identify as male or female.
Race/Ethnicity, Customized American Indian or Alaska Native	4 Participants n=658 Participants	2 Participants n=654 Participants	6 Participants n=1312 Participants
Race/Ethnicity, Customized Asian/South Asian	204 Participants n=658 Participants	206 Participants n=654 Participants	410 Participants n=1312 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	5 Participants n=658 Participants	4 Participants n=654 Participants	9 Participants n=1312 Participants
Race/Ethnicity, Customized Black or African American	28 Participants n=658 Participants	24 Participants n=654 Participants	52 Participants n=1312 Participants
Race/Ethnicity, Customized White	363 Participants n=658 Participants	379 Participants n=654 Participants	742 Participants n=1312 Participants
Race/Ethnicity, Customized Hispanic or Latino	37 Participants n=658 Participants	36 Participants n=654 Participants	73 Participants n=1312 Participants
Race/Ethnicity, Customized Middle Eastern	14 Participants n=658 Participants	9 Participants n=654 Participants	23 Participants n=1312 Participants
Race/Ethnicity, Customized Unknown/Not Reported	12 Participants n=658 Participants	10 Participants n=654 Participants	22 Participants n=1312 Participants
Region of Enrollment Canada	30 Participants n=658 Participants	29 Participants n=654 Participants	59 Participants n=1312 Participants
Region of Enrollment United States	628 Participants n=658 Participants	625 Participants n=654 Participants	1253 Participants n=1312 Participants

PRIMARY outcome

Timeframe: 14 days

Number of participants at 14 days post enrollment with active COVID19 disease among those who were asymptomatic at baseline.

Outcome measures

Measure	Treatment n=414 Participants 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	Placebo n=407 Participants 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
Number of Participants With Active COVID-19 Disease at Day 14 Among Those Who Were Asymptomatic at Baseline	49 Participants	58 Participants

PRIMARY outcome

Timeframe: baseline and 14 days

Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)

Outcome measures

Measure	Treatment n=212 Participants 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	Placebo n=211 Participants 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
Change in Disease Severity Over 14 Days Among Those Who Are Symptomatic at Baseline	-2.6 score on a scale Standard Error .12	-2.33 score on a scale Standard Error .12

SECONDARY outcome

Timeframe: 14 days

Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.

Outcome measures

Measure	Treatment n=645 Participants 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	Placebo n=641 Participants 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
Rate of Hospitalization	5 Participants	9 Participants

SECONDARY outcome

Timeframe: Approximately 30 days

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.

Outcome measures

Measure	Treatment n=645 Participants 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	Placebo n=641 Participants 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
Rate of Death	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 14 days

Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.

Outcome measures

Measure	Treatment n=414 Participants 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	Placebo n=407 Participants 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
Rate of Confirmed SARS-CoV-2 Detection	11 Participants	9 Participants

SECONDARY outcome

Timeframe: 14 days

Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID-19 infection.

Outcome measures

Measure	Treatment n=414 Participants 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	Placebo n=407 Participants 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
Occurrence of Symptoms Compatible With COVID-19 (Possible Disease)	48 Participants	55 Participants

SECONDARY outcome

Timeframe: 14 days

Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.

Outcome measures

Measure	Treatment n=645 Participants 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	Placebo n=641 Participants 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
Rate of All-Cause Study Medicine Discontinuation or Withdrawal	97 Participants	63 Participants

SECONDARY outcome

Timeframe: 5 and 14 days

Population: Early preemptive treatment trial (n=423 symptomatic participants with data)

Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)

Outcome measures

Measure	Treatment n=212 Participants 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	Placebo n=211 Participants 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 Symptom Severity at 5 and 14 Days Day 5	-2.22 score on a scale Interval -2.53 to -1.9	-2.05 score on a scale Interval -2.37 to -1.73
Overall Symptom Severity at 5 and 14 Days Day 14	-3.36 score on a scale Interval -3.62 to -3.09	-3.08 score on a scale Interval -3.35 to -2.81

SECONDARY outcome

Timeframe: 14 days

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.

Outcome measures

Measure	Treatment n=231 Participants 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	Placebo n=234 Participants 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
Number of Participants With Severe COVID-19 Disease at 14 Days Among Those Who Are Symptomatic at Trial Entry	5 Participants	8 Participants

Adverse Events

Treatment

Serious events: 6 serious events

Other events: 367 other events

Deaths: 1 deaths

Placebo

Serious events: 11 serious events

Other events: 148 other events

Deaths: 1 deaths

Serious adverse events

Measure	Treatment n=658 participants at risk 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	Placebo n=654 participants at risk 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
Infections and infestations COVID-related hospitalization	0.91% 6/658 • Number of events 6 • Approximately 30-days 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.	1.4% 9/654 • Number of events 9 • Approximately 30-days 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.
Cardiac disorders Hospitalizations not related to COVID or study medicine	0.00% 0/658 • Approximately 30-days 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.	0.31% 2/654 • Number of events 2 • Approximately 30-days 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.

Other adverse events

Measure	Treatment n=658 participants at risk 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	Placebo n=654 participants at risk 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
Gastrointestinal disorders Nausea or upset stomach	22.2% 146/658 • Number of events 146 • Approximately 30-days 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.	8.1% 53/654 • Number of events 53 • Approximately 30-days 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.
Gastrointestinal disorders Diarrhea, abdominal pain, vomiting	19.9% 131/658 • Number of events 131 • Approximately 30-days 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.	5.4% 35/654 • Number of events 35 • Approximately 30-days 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.
General disorders Irritability, dizziness, vertigo	5.9% 39/658 • Number of events 39 • Approximately 30-days 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.	4.0% 26/654 • Number of events 26 • Approximately 30-days 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.
Ear and labyrinth disorders Tinnitus	2.4% 16/658 • Number of events 16 • Approximately 30-days 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.	1.2% 8/654 • Number of events 8 • Approximately 30-days 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.
General disorders Headache	2.3% 15/658 • Number of events 15 • Approximately 30-days 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.	1.2% 8/654 • Number of events 8 • Approximately 30-days 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.
Eye disorders Visual changes	1.1% 7/658 • Number of events 7 • Approximately 30-days 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.	0.76% 5/654 • Number of events 5 • Approximately 30-days 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.
Skin and subcutaneous tissue disorders Skin reaction	1.5% 10/658 • Number of events 10 • Approximately 30-days 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.	0.61% 4/654 • Number of events 4 • Approximately 30-days 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.
General disorders Taste change or dry mouth	0.46% 3/658 • Number of events 3 • Approximately 30-days 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.	0.46% 3/654 • Number of events 3 • Approximately 30-days 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.
Immune system disorders Allergic reaction (non-anaphylaxis)	0.91% 6/658 • Number of events 6 • Approximately 30-days 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.	0.15% 1/654 • Number of events 1 • Approximately 30-days 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.
General disorders Hot flashes, night sweats, palpitations	0.30% 2/658 • Number of events 2 • Approximately 30-days 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.	0.15% 1/654 • Number of events 1 • Approximately 30-days 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.
General disorders Fatigue	0.15% 1/658 • Number of events 1 • Approximately 30-days 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.	0.15% 1/654 • Number of events 1 • Approximately 30-days 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.
Psychiatric disorders Panic	0.00% 0/658 • Approximately 30-days 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.	0.15% 1/654 • Number of events 1 • Approximately 30-days 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.
General disorders Other	0.15% 1/658 • Number of events 1 • Approximately 30-days 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.	0.31% 2/654 • Number of events 2 • Approximately 30-days 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.

Additional Information

David Boulware, MD, MPH

University of Minnesota

Phone: 6125552020

Email: covid19@umn.edu

Results disclosure agreements

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