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Atovaquone for Treatment of COVID-19

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: NCT04456153
Recruitment Status : Completed
First Posted : July 2, 2020
Results First Posted : December 14, 2021
Last Update Posted : December 14, 2021
Sponsor:
Information provided by (Responsible Party):
Mamta K. Jain, MD,MPH, University of Texas Southwestern Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition COVID-19
Interventions Drug: Experimental Group
Drug: Placebo Group
Enrollment 60
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Standard of Care Therapy With Matching Placebo Standard of Care Therapy With Atovaquone
Hide Arm/Group Description

The second treatment group will receive continued standard of care therapy together with matching placebo.

Placebo Group: Continued standard of care therapy together with matching placebo

The first treatment group will receive continued standard of care therapy together with an oral dose of 1500 mg atovaquone twice daily (administered with a meal or snack) for up to 10 days.

Experimental Group: Continued standard of care therapy together with an oral dose of 1500 mg atovaquone twice daily (administered with a meal or snack) for up to 10 days

Period Title: Overall Study
Started 19 41
Completed 19 41
Not Completed 0 0
Arm/Group Title Standard of Care Therapy With Atovaquone Standard of Care Therapy With Matching Placebo Total
Hide Arm/Group Description The first treatment group will receive continued standard of care therapy together with an oral dose of 1500 mg atovaquone twice daily (administered with a meal or snack) for up to 10 days. The second treatment group will receive continued standard of care therapy together with matching placebo. Total of all reporting groups
Overall Number of Baseline Participants 41 19 60
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 41 participants 19 participants 60 participants
51.64
(42.5 to 60.8)
49.4
(41 to 59.6)
50.9
(41.9 to 59.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 19 participants 60 participants
Female
15
  36.6%
7
  36.8%
22
  36.7%
Male
26
  63.4%
12
  63.2%
38
  63.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 19 participants 60 participants
Hispanic or Latino
29
  70.7%
13
  68.4%
42
  70.0%
Not Hispanic or Latino
12
  29.3%
6
  31.6%
18
  30.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 19 participants 60 participants
non-Hispanic White
31
  75.6%
15
  78.9%
46
  76.7%
Black
6
  14.6%
2
  10.5%
8
  13.3%
other
4
   9.8%
2
  10.5%
6
  10.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 41 participants 19 participants 60 participants
41 19 60
log 10 viral load (copies/mL)  
Mean (Standard Deviation)
Unit of measure:  Log 10 RNA copies/mL
Number Analyzed 41 participants 19 participants 60 participants
atovaquone 5.25  (0.278) 0  (0) 5.25  (0.278)
Placebo 0  (0) 4.79  (0.408) 4.79  (0.408)
1.Primary Outcome
Title Primary Analysis
Hide Description Between group differences in viral load (Log copy number/ml) using generalized linear mixed-effect models of repeated measures (GLMM), using data from all available samples
Time Frame Day 1 to Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
Change in viral load from day 1 to day 10 between intervention arm and placebo
Arm/Group Title Overall Group Atovaquone Group With Standard of Care Treatment Placebo Plus Standard of Care
Hide Arm/Group Description:
Comparison of experimental group to placebo
This arm received atovaquone 2: 1 in addition to the standard of care.
This arm received matched placebo in addition to the standard of care.
Overall Number of Participants Analyzed 60 41 19
Mean (95% Confidence Interval)
Unit of Measure: log 10 (copies/mL)
-1.906
(-3.090 to 0.123)
2.629
(1.652 to 3.606)
4.073
(3.131 to 5.015)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atovaquone Group With Standard of Care Treatment, Placebo Plus Standard of Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.170
Comments [Not Specified]
Method GLMM
Comments [Not Specified]
2.Secondary Outcome
Title Secondary Between Group Differences in Viral Load
Hide Description Change in viral load at Day 3, 5, and 7 days. This shows the group differences between intervention and placebo and log 10 viral load at specific days 3, 5, and 7 for atovaquone arm and placebo arm.
Time Frame baseline to day7
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Difference Between Atovaquone and Placebo Atovaquone Plus Standard of Care Placebo Plus Standard of Care
Hide Arm/Group Description:
Comparison of experimental group to placebo
Log 10 viral load of atovaquone group at Day 3, 5, 7
Log 10 viral load of placebo group at Day 3, 5, and 7
Overall Number of Participants Analyzed 60 41 19
Mean (95% Confidence Interval)
Unit of Measure: log 10 (copies/mL)
day 1 to 3
0.129
(-0.571 to 0.829)
5.342
(4.548 to 6.135)
4.406
(3.609 to 5.203)
day 1 to 5
0.107
(-0.610 to 0.823)
4.329
(3.785 to 4.874)
3.760
(2.948 to 4.572)
day 1 to 7
-0.766
(-1.534 to 0.002)
3.804
(3.230 to 4.378)
4.108
(3.270 to 4.946)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Difference Between Atovaquone and Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.051
Comments [Not Specified]
Method GLMM
Comments [Not Specified]
3.Secondary Outcome
Title Change in Viral Load at Day 10 Stratified by Sex
Hide Description Between group differences in viral load (Log copy number/ml) using GLMM stratified by
Time Frame baseline to day 10
Hide Outcome Measure Data
Hide Analysis Population Description
Between group differences Day 1 to day 10
Arm/Group Title Stratified by Sex: Men Stratified by Sex: Women
Hide Arm/Group Description:
Comparison of change in viral load from Day 1 to day 10 between placebo and atovaquone
Comparison of change in viral load from Day 1 to day 10 between placebo and atovaquone
Overall Number of Participants Analyzed 38 22
Mean (95% Confidence Interval)
Unit of Measure: log 10 viral load (copies/mL)
-1.8732
(-3.8342 to 0.08779)
0.555
(-1.9539 to 3.0639)
4.Secondary Outcome
Title Percentage With 2 Log Viral Load Drop at Day 3
Hide Description Between group comparison of time to drop in viral load (Log copy number/ml) of 2 log units using Kaplan-Meier estimation. Examined the percentage of participants who achieved this viral load drop in 3 days.
Time Frame baseline to day 3
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atovaquone Placebo
Hide Arm/Group Description:
Atovaquone plus standard of care therapy. Proportion who had 2 log drop at Day 3
Matching placebo plus standard of care therapy. Proportion who had 2 log drop at Day 3
Overall Number of Participants Analyzed 41 19
Measure Type: Number
Unit of Measure: percentage of participants
15 20
5.Secondary Outcome
Title Number of Participants With Change in Ordinal Scale ≥2 Points by Day 15.
Hide Description Ordinal scale 1 indicated death, and higher scores were various degrees of hospitalizations and incapacity to being out of hospital. Ordinal Scale 1-7 with higher score indicating improvement in clinical status. Change of ≥2 points on the ordinal scale by Day 15 using chi-square analysis
Time Frame Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atovaquone Placebo
Hide Arm/Group Description:
Atovaquone group at Day 15. Number of participants who had > or = 2 point change in ordinal score
Matching placebo at Day 15. Number of participants who had > or = 2 point change in ordinal score
Overall Number of Participants Analyzed 40 17
Measure Type: Count of Participants
Unit of Measure: Participants
25
  62.5%
9
  52.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atovaquone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.68
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
6.Secondary Outcome
Title Area Under the Curve Copies/ml*Day at Day 7
Hide Description This is a alternative method of measurement of area which examines the viral load ( copies/ml )(y-axis) by day (x-axis) using the trapezoidal method. The area under the curve was calculated via the trapezoidal rule. As such, this is a numeric value that is different than the traditional use of the term "mean" or "median." However, in order to calculate a measure of error associated with this quantity, bootstrapping with 500 replications would need to be performed to assess statistical significance or lack thereof. The mean of the bootstrap samples could be reported as the "mean area under the curve."
Time Frame day 7
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atovaquone Placebo
Hide Arm/Group Description:
Atovaquone plus standard of care
Matching placebo plus standard of care
Overall Number of Participants Analyzed 41 19
Measure Type: Number
Unit of Measure: copies/mL*day
38.39 36.09
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atovaquone, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76
Comments [Not Specified]
Method trapezoidal method
Comments [Not Specified]
7.Secondary Outcome
Title Stratifed by Remdesivir
Hide Description change in log RNA 10 day 1 to 10 stratified by remdesivir by GLMM
Time Frame day 10
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Stratified With Remdesivir Stratified Without Remdesivir
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Participants who received remdesivir as part of standard of care
Participants who did not receive remdesivir as part of standard of care
Overall Number of Participants Analyzed 36 24
Mean (95% Confidence Interval)
Unit of Measure: log 10 RNA copies/mL
-0.754
(-2.440 to 0.933)
-2.010
(-4.513 to 0.494)
Time Frame During hospitalization for an average of 10 days
Adverse Event Reporting Description Collected grade 3 or 4 adverse events
 
Arm/Group Title Atovaquone Placebo
Hide Arm/Group Description Atovaquone plus standard of care. Grade 3 and 4 adverse events were collected. Matching placebo plus standard of care
All-Cause Mortality
Atovaquone Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   6/41 (14.63%)      2/19 (10.53%)    
Hide Serious Adverse Events
Atovaquone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/41 (17.07%)      3/19 (15.79%)    
Respiratory, thoracic and mediastinal disorders     
hypoxic respiratory failure *  7/41 (17.07%)  7 3/19 (15.79%)  3
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Atovaquone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/41 (4.88%)      0/19 (0.00%)    
Gastrointestinal disorders     
Transaminitis *  2/41 (4.88%)  2 0/19 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
This study was not powered for clinical endpoints.
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: Dr. Mamta K. Jain
Organization: UT Southwestern Medical Center
Phone: 2140648-9914
EMail: mamta.jain@utsouthwestern.edu
Layout table for additonal information
Responsible Party: Mamta K. Jain, MD,MPH, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT04456153    
Other Study ID Numbers: STU-2020-0707
First Submitted: June 30, 2020
First Posted: July 2, 2020
Results First Submitted: November 10, 2021
Results First Posted: December 14, 2021
Last Update Posted: December 14, 2021