Trial Outcomes & Findings for StAT-TB (Statin Adjunctive Therapy for TB): A Phase 2b Dose-finding Study of Pravastatin in Adults With Tuberculosis (NCT NCT03882177)

Last Updated: 2023-09-18

Results Overview

Graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

Measured through Day 30

Results posted on

2023-09-18

Participant Flow

Participant milestones

Participant milestones
Measure	Arm 1: Pravastatin (40 mg) and Rifafour Participants will receive pravastatin (40 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. Pravastatin: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 2: Pravastatin (80 mg) and Rifafour Participants will receive pravastatin (80 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. Pravastatin: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.
Overall Study STARTED	10	6
Overall Study COMPLETED	10	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

StAT-TB (Statin Adjunctive Therapy for TB): A Phase 2b Dose-finding Study of Pravastatin in Adults With Tuberculosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: Pravastatin (40 mg) and Rifafour n=10 Participants Participants will receive pravastatin (40 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. Pravastatin: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 2: Pravastatin (80 mg) and Rifafour n=6 Participants Participants will receive pravastatin (80 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. Pravastatin: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 3: Pravastatin (120 mg) and Rifafour Participants will receive pravastatin (120 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. (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: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 4: Pravastatin (160 mg) and Rifafour Participants will receive pravastatin (160 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. (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: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	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) 45-49 kg	1 Participants n=5 Participants	0 Participants n=7 Participants	—	—	1 Participants n=21 Participants
Weight at Baseline (kg) 50-59 kg	7 Participants n=5 Participants	4 Participants n=7 Participants	—	—	11 Participants n=21 Participants
Weight at Baseline (kg) 60-69 kg	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: Measured through Day 30

Population: Participants were not enrolled in Arms 3 and 4 due to early termination.

Graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

Outcome measures

Outcome measures
Measure	Arm 1: Pravastatin (40 mg) and Rifafour n=10 Participants Participants will receive pravastatin (40 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. Pravastatin: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 2: Pravastatin (80 mg) and Rifafour n=6 Participants Participants will receive pravastatin (80 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. Pravastatin: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 3: Pravastatin (120 mg) and Rifafour Participants will receive pravastatin (120 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. (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: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 4: Pravastatin (160 mg) and Rifafour Participants will receive pravastatin (160 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. (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: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.
Frequency of Grade 3 or Higher Adverse Events	8 AEs Grade 3 or Higher	4 AEs Grade 3 or Higher	—	—

SECONDARY outcome

Timeframe: Measured through Day 14

Population: Participants were not enrolled in Arms 3 and 4 due to early termination.

(Other than new recognition of participant ineligibility based on absence of M. tuberculosis growth in baseline sputum cultures, or growth of M. tuberculosis resistant to rifampin by GeneXpert)

Outcome measures

Outcome measures
Measure	Arm 1: Pravastatin (40 mg) and Rifafour n=10 Participants Participants will receive pravastatin (40 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. Pravastatin: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 2: Pravastatin (80 mg) and Rifafour n=6 Participants Participants will receive pravastatin (80 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. Pravastatin: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 3: Pravastatin (120 mg) and Rifafour Participants will receive pravastatin (120 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. (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: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 4: Pravastatin (160 mg) and Rifafour Participants will receive pravastatin (160 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. (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: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.
Number of Participants Who Permanently Discontinue Assigned Study Regimen for Any Reason	10 Participants	6 Participants	0 Participants	0 Participants

Adverse Events

Arm 1: Pravastatin (40 mg) and Rifafour

Serious events: 4 serious events

Other events: 5 other events

Deaths: 0 deaths

Arm 2: Pravastatin (80 mg) and Rifafour

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Arm 3: Pravastatin (120 mg) and Rifafour

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm 4: Pravastatin (160 mg) and Rifafour

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm 1: Pravastatin (40 mg) and Rifafour n=10 participants at risk Participants will receive pravastatin (40 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. Pravastatin: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 2: Pravastatin (80 mg) and Rifafour n=6 participants at risk Participants will receive pravastatin (80 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. Pravastatin: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 3: Pravastatin (120 mg) and Rifafour Participants will receive pravastatin (120 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. (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: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 4: Pravastatin (160 mg) and Rifafour Participants will receive pravastatin (160 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. (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: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.
Investigations Elevated Uric Acid	30.0% 3/10 • Number of events 3 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	16.7% 1/6 • Number of events 1 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	— 0/0 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	— 0/0 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Investigations Elevated liver enzymes (ALT/AST)	10.0% 1/10 • Number of events 1 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	0.00% 0/6 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	— 0/0 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	— 0/0 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

Other adverse events

Other adverse events
Measure	Arm 1: Pravastatin (40 mg) and Rifafour n=10 participants at risk Participants will receive pravastatin (40 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. Pravastatin: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 2: Pravastatin (80 mg) and Rifafour n=6 participants at risk Participants will receive pravastatin (80 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. Pravastatin: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 3: Pravastatin (120 mg) and Rifafour Participants will receive pravastatin (120 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. (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: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.	Arm 4: Pravastatin (160 mg) and Rifafour Participants will receive pravastatin (160 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. (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: Tablets, administered orally Rifafour: Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally Vitamin B6: Administered orally.
Investigations Decreased hemoglobin level	10.0% 1/10 • Number of events 1 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	0.00% 0/6 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	— 0/0 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	— 0/0 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Investigations Elevated creatinine kinase	10.0% 1/10 • Number of events 1 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	0.00% 0/6 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	— 0/0 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	— 0/0 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Investigations Elevated liver enzymes (ALT/AST)	10.0% 1/10 • Number of events 1 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	0.00% 0/6 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	— 0/0 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	— 0/0 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Investigations Elevated uric acid	20.0% 2/10 • Number of events 2 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	50.0% 3/6 • Number of events 3 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	— 0/0 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017	— 0/0 • Measured up to 30 days Adverse Events and Serious Adverse Events graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

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