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

NCT03882177 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: StAT-TB38558
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of pravastatin adjunctive therapy when combined with the standard tuberculosis (TB) treatment regimen in adults with TB.

Conditions

Tuberculosis; Pulmonary Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Frequency of Grade 3 or Higher Adverse Events

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

  Measured through Day 30

Secondary Outcomes (1)

• Number of Participants Who Permanently Discontinue Assigned Study Regimen for Any Reason

  Measured through Day 14

Study Arms (4)

Arm 1: Pravastatin (40 mg) and Rifafour

EXPERIMENTAL

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.

Drug: Pravastatin; Drug: Rifafour; Dietary Supplement: Vitamin B6

Arm 2: Pravastatin (80 mg) and Rifafour

EXPERIMENTAL

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.

Drug: Pravastatin; Drug: Rifafour; Dietary Supplement: Vitamin B6

Arm 3: Pravastatin (120 mg) and Rifafour

EXPERIMENTAL

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.)

Drug: Pravastatin; Drug: Rifafour; Dietary Supplement: Vitamin B6

Arm 4: Pravastatin (160 mg) and Rifafour

EXPERIMENTAL

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.)

Drug: Pravastatin; Drug: Rifafour; Dietary Supplement: Vitamin B6

Interventions

Pravastatin DRUG

Tablets, administered orally

Arm 1: Pravastatin (40 mg) and Rifafour; Arm 2: Pravastatin (80 mg) and Rifafour; Arm 3: Pravastatin (120 mg) and Rifafour; Arm 4: Pravastatin (160 mg) and Rifafour

Rifafour DRUG

Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally

Arm 1: Pravastatin (40 mg) and Rifafour; Arm 2: Pravastatin (80 mg) and Rifafour; Arm 3: Pravastatin (120 mg) and Rifafour; Arm 4: Pravastatin (160 mg) and Rifafour

Vitamin B6 DIETARY_SUPPLEMENT

Administered orally.

Arm 1: Pravastatin (40 mg) and Rifafour; Arm 2: Pravastatin (80 mg) and Rifafour; Arm 3: Pravastatin (120 mg) and Rifafour; Arm 4: Pravastatin (160 mg) and Rifafour

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older
• Clinical signs and symptoms of pulmonary tuberculosis
• Abnormal chest radiograph consistent with pulmonary tuberculosis
• At least one sputum positive for M. tuberculosis by Xpert MTB/RIF with a cycle threshold (Ct) less than 28.
• Documentation of HIV status
• Weight greater than or equal to 45 kg
• Karnofsky score of at least 60
• Ability to provide informed consent
• Ability to adhere to study follow-up visits
• Negative pregnancy test in women of child-bearing age
• Ability to adhere to contraceptive requirements and willing to use two forms of contraception: 1) a double barrier method to prevent pregnancy (i.e. use of a condom with either diaphragm or cervical cap) or 2) use of an intrauterine device in combination with a barrier contraceptive. The participant must be willing to continue these contraceptive measures throughout the duration of the study and until one week after the last dose of study medication or one week after discontinuation from study medication in case of premature discontinuation.
• Five days or fewer of anti-tuberculosis treatment within the previous 3 months

You may not qualify if:

• A history of severe adverse reactions to any statin or any other study agent or contraindications to use of statins.
• Current use of statins or other lipid-lower agents;
• Clinical indication for statin therapy based on cardiovascular risk:
• Familial hypercholesterolemia
• Previous history of myocardial infarction or stroke
• For HIV-positive individuals, a CD4+ T-cell count less than 350/mm\^3
• Use of antiretroviral drugs
• Hemoglobin concentration less than 8 g/dL;
• Baseline creatinine kinase elevation more than three times the upper limit of normal
• Abnormal baseline laboratory values
• Baseline alanine aminotransferase (ALT) concentration more than 2.5 times the upper limit of normal (Grade 1)
• Serum creatinine concentration more than twice the upper limit of normal;
• Serum total bilirubin level greater than twice the upper limit of normal
• Platelet count less than 100,000/mm\^3
• Absolute neutrophil count (ANC) less than 1,000/mm\^3

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

PHRU Non-Network CRS

Johannesburg, Gauteng, 1864, South Africa

Location

MeSH Terms

Conditions

Tuberculosis; Tuberculosis, Pulmonary

Interventions

Pravastatin; Vitamin B 6

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Picolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Petros C. Karakousis, MD
• Organization: Johns Hopkins University School of Medicine

petros@jhmi.edu

410-502-8233

Study Officials

• Petros C. Karakousis, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Richard E. Chaisson, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Neil Martinson, MD, MPH

  University of Witwatersrand, South Africa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2019
• First Posted: March 20, 2019
• Study Start: February 21, 2020
• Primary Completion: May 12, 2022
• Study Completion: December 31, 2022
• Last Updated: September 18, 2023
• Results First Posted: September 18, 2023

Record last verified: 2023-08

Locations

ZA (1)