Trial

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

Study Director
Petros C. Karakousis, MD Johns Hopkins University
Start Date
2 / 2020
Trial Phase
Phase II
Trial Status
in data analysis
Current Enrollment
35
Target Enrollment
35 Participants
Overview

This study will assess the safety, tolerability, and pharmacokinetics of pravastatin adjunctive therapy when combined with the standard TB treatment regimen in adults with drug-sensitive TB. The pharmacokinetic data for pravastatin will be used to choose a dose to be studied as adjunctive TB treatment in subsequent trials.

This study is a dose-escalation trial, and participants will be sequentially enrolled into four study arms. Participants will receive standard anti-TB therapy (Rifafour) and pravastatin daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15.

Total study duration for participants will be 30 days, during which time participants will attend several study visits. Study visits may include sputum specimen collection, blood and urine collection, lung function testing, and pharmacokinetic assessments. All study participants will be referred appropriately to continue standard TB treatment at study completion.

 

Experimental: 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.

Experimental: 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.

Experimental: 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.)

Experimental: 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.)

Primary Outcome Measures  :

  1. Frequency of Grade 3 or higher adverse events [ Time Frame: Measured through Day 30 ]

Secondary Outcome Measures  :

  1. Number of participants who permanently discontinue assigned study regimen for any reason [ Time Frame: Measured through Day 14 ]