Trial Outcomes & Findings for Statin Adjunctive Therapy for TB (NCT NCT03456102)
NCT ID: NCT03456102
Last Updated: 2023-06-28
Results Overview
Safety of escalating doses of pravastatin (40 mg - 160 mg) when co-administered with rifampin, as evidenced by number of Grade 3 or higher adverse events.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
16 participants
Primary outcome timeframe
Up to 30 days
Results posted on
2023-06-28
Participant Flow
Study participants were recruited from clinics in Soweto, South Africa by the study team at the PHRU, Chris Hani Baragwanath Academic Hospital, Soweto, South Africa. Participants were recruited based on having a sputum specimen that is positive for TB by GeneXpert MTB/RIF.
Participant milestones
| Measure |
Pravastatin 40 mg
Pravastatin 40 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 4 will only be recruited if pravastatin 80 mg is not tolerated as specified in protocol.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 80 mg
Pravastatin 80 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 2 will only be recruited if pravastatin 80 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 120 mg
Pravastatin 120 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 3 will only be recruited if pravastatin 120 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 160 mg
Pravastatin 160 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
6
|
0
|
0
|
|
Overall Study
COMPLETED
|
10
|
6
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Statin Adjunctive Therapy for TB
Baseline characteristics by cohort
| Measure |
Pravastatin 40 mg
n=10 Participants
Pravastatin 40 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 4 will only be recruited if pravastatin 80 mg is not tolerated as specified in protocol.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 80 mg
n=6 Participants
Pravastatin 80 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 2 will only be recruited if pravastatin 80 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 120 mg
Pravastatin 120 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 3 will only be recruited if pravastatin 120 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 160 mg
Pravastatin 160 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
26.70 years
STANDARD_DEVIATION 5.35 • n=5 Participants
|
26.83 years
STANDARD_DEVIATION 7.03 • n=7 Participants
|
—
|
—
|
26.75 years
STANDARD_DEVIATION 5.80 • n=21 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
—
|
—
|
5 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
—
|
—
|
11 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
African/Black
|
10 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
—
|
—
|
16 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Coloured
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
—
|
0 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Indian/Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
—
|
0 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
—
|
0 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
—
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
South Africa
|
10 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
—
|
—
|
16 Participants
n=21 Participants
|
|
Weight at Baseline (kg)
45-49kg
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
—
|
1 Participants
n=21 Participants
|
|
Weight at Baseline (kg)
50-59kg
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
—
|
—
|
11 Participants
n=21 Participants
|
|
Weight at Baseline (kg)
60-69kg
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
—
|
—
|
4 Participants
n=21 Participants
|
|
HIV Status
Negative
|
10 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
—
|
—
|
16 Participants
n=21 Participants
|
|
HIV Status
Positive
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
—
|
—
|
0 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Up to 30 daysPopulation: Participants were not enrolled in Arms 3 and 4 due to early termination.
Safety of escalating doses of pravastatin (40 mg - 160 mg) when co-administered with rifampin, as evidenced by number of Grade 3 or higher adverse events.
Outcome measures
| Measure |
Pravastatin 40 mg
n=10 Participants
Pravastatin 40 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 80 mg
n=6 Participants
Pravastatin 80 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 2 will only be recruited if pravastatin 40 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 120 mg
Pravastatin 120 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 3 will only be recruited if pravastatin 80 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 160 mg
Pravastatin 160 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 4 will only be recruited if pravastatin 120 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
|---|---|---|---|---|
|
Safety of Escalating Doses of Pravastatin as Assessed by Number of Adverse Events
|
8 AEs Grade 3 or Higher
|
4 AEs Grade 3 or Higher
|
—
|
—
|
Adverse Events
Pravastatin 40 mg
Serious events: 4 serious events
Other events: 5 other events
Deaths: 0 deaths
Pravastatin 80 mg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Pravastatin 120 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Pravastatin 160 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pravastatin 40 mg
n=10 participants at risk
Pravastatin 40 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 80 mg
n=6 participants at risk
Pravastatin 80 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 2 will only be recruited if pravastatin 40 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 120 mg
Pravastatin 120 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 3 will only be recruited if pravastatin 80 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 160 mg
Pravastatin 160 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 4 will only be recruited if pravastatin 120 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
|---|---|---|---|---|
|
Investigations
Elevated Uric Acid
|
30.0%
3/10 • Number of events 3 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
16.7%
1/6 • Number of events 1 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
—
0/0 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
—
0/0 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
|
Investigations
Elevated liver enzymes (ALT/AST)
|
10.0%
1/10 • Number of events 1 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
0.00%
0/6 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
—
0/0 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
—
0/0 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
Other adverse events
| Measure |
Pravastatin 40 mg
n=10 participants at risk
Pravastatin 40 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 80 mg
n=6 participants at risk
Pravastatin 80 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 2 will only be recruited if pravastatin 40 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 120 mg
Pravastatin 120 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 3 will only be recruited if pravastatin 80 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
Pravastatin 160 mg
Pravastatin 160 mg, isoniazid 300 mg, rifampin 450 mg (weight \<50 kg) or 600 mg (weight \>50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 4 will only be recruited if pravastatin 120 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
|
|---|---|---|---|---|
|
Investigations
Elevated liver enzymes (ALT/AST)
|
10.0%
1/10 • Number of events 1 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
0.00%
0/6 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
—
0/0 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
—
0/0 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
|
Investigations
Elevated creatinine kinase
|
10.0%
1/10 • Number of events 1 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
0.00%
0/6 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
—
0/0 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
—
0/0 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
|
Investigations
Elevated uric acid
|
20.0%
2/10 • Number of events 2 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
50.0%
3/6 • Number of events 3 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
—
0/0 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
—
0/0 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
|
Investigations
Decreased hemoglobin level
|
10.0%
1/10 • Number of events 1 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
0.00%
0/6 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
—
0/0 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
—
0/0 • Up to 5 months.
No patients were enrolled in Study Arms 3 and 4 due to early termination.
|
Additional Information
Petros C. Karakousis, MD
Johns Hopkins University School of Medicine
Phone: 410-502-8233
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place