Using Atorvastatin to treat Pulmonary Tuberculosis

Atorvastatin-containing Treatment Regimens for Pulmonary Tuberculosis: A Randomized, Open-label, Controlled phase2C/3 Clinical Trial

This study is testing if adding Atorvastatin, a cholesterol-lowering drug, can help people with pulmonary tuberculosis get better when they start treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 440 (estimated)
• Ages: 12 Years to 65 Years
• Sex: All
• Sponsor: Obafemi Awolowo University Teaching Hospital (Academic / other)
• Locations: 8 sites (Zaria, Kaduna State and 7 other locations)
• Trial ID: NCT06199921 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of Atorvastatin, a cholesterol-lowering medication, as an adjunct treatment for patients with pulmonary tuberculosis. The study aims to evaluate the efficacy of different doses of Atorvastatin (20mg, 40mg, and 60mg) in improving treatment outcomes for individuals diagnosed with TB. Participants must be treatment-naive and meet specific inclusion criteria, including age and HIV status. The trial will be conducted at multiple locations in Nigeria, focusing on areas with a high burden of tuberculosis.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 12 years and older who have suspected pulmonary tuberculosis and are treatment-naive.

Not a fit: Patients with advanced HIV disease or those who have previously received treatment for tuberculosis may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could enhance the effectiveness of current tuberculosis therapies and improve patient outcomes.

How similar studies have performed: While the use of statins in tuberculosis treatment is an emerging area of interest, this specific approach with Atorvastatin is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

Individuals must meet all the following inclusion criteria in order to participate in this study:

A. Suspected pulmonary tuberculosis plus one or both of the following: a) at least one sputum specimen positive for acid-fast bacilli on smear microscopy OR b) at least one sputum specimen positive for M. tuberculosis by Xpert MTB/RIF testing, with semiquantitative result of 'medium' or 'high' and rifampicin resistance not detected.

B. Treatment naive

C. Age twelve years or older

D. A verifiable address or residence location that is readily accessible for visiting, and willingness to inform the study team of any change of address during the treatment and follow-up period.

E. Documented HIV infection status.

F. Documented blood sugar level/ Diabetes

G. For HIV-positive individuals, CD4 T cell count greater than or equal to 100 cells/mm3 based on testing performed at or within 30 days prior to screening.

H. Laboratory parameters done at or within 14 days prior to screening:

* Serum or plasma alanine aminotransferase (ALT) less than or equal to 3 times the upper limit of normal
* Serum or plasma total bilirubin less than or equal to 2.5 times the upper limit of normal
* Serum or plasma creatinine level less than or equal to 2 times the upper limit of normal
* Serum or plasma potassium level greater than or equal to 3.5 meq/L
* Hemoglobin level of 7.0 g/dL or greater
* Platelet count of 100,000/mm3 or greater

I. For women of childbearing potential, a negative pregnancy test at or within seven (7) days prior to screening

J. Written informed consent

Exclusion Criteria:

Individuals with any of the following exclusion criteria at the time of enrollment or initiation of study drugs will be excluded.

A. Pregnant or breast-feeding

B. Unable to take oral medications

C. Those already on treatment for tuberculosis

D. Weight less than 40.0 kg

E. Known allergy or intolerance to any of the study medications

F. Individuals will be excluded from enrollment if, at the time of enrollment, their M. tuberculosis isolate is already known to be resistant to any one or more of the following: rifampin, isoniazid, pyrazinamide,or ethambutol,

G. .Evidence of clinically significant metabolic or co morbid medical conditions ; malignancy; or other diseases like history of or current cardiovascular disorder such as heart failure, coronary heart disease, arrhythmia.

H. Known or family history of bleeding disorders. I. Any renal impairment characterized by serum creatinine clearance of 1.5 x upper limit of normal of the clinical laboratory reference range at screening.

J. Myositis and or Creatinine phosphokinase three times upper limit of normal K. Other medical conditions, that, in the investigator's judgment, make study participation not in the individual's best interest.

Criteria for Exclusion after Enrollment ('Late Exclusion')

Microbiological confirmation of drug-susceptible tuberculosis is not expected always to be available at the time of enrollment. Enrolled individuals who are subsequently determined to meet either of the following criteria will be classified as 'late exclusions' and study treatment will be discontinued:

A. Screening, baseline, and Week 2 study visit sputum cultures all fail to grow M. tuberculosis.

B. M. tuberculosis cultured or detected through molecular assays (Cepheid Xpert MTB/RIF or Hain MTBDRplus assays) from sputum obtained around the time of study entry is determined to be resistant to one or more of isoniazid, rifampin, or fluoroquinolones.

Where this trial is running

Zaria, Kaduna State and 7 other locations

• National Tuberculosis Reference Laboratory — Zaria, Kaduna State, Nigeria (Recruiting)
• Federal Teaching Hospital — Katsina, Katsina State, Nigeria (Recruiting)
• Federal Medical Center — Keffi, Nasarawa State, Nigeria (Recruiting)
• Obafemi Awolowo University Teaching Hospitals Complex — Ile-Ife, Osun State, Nigeria (Recruiting)
• Bowen University Teaching Hospital — Iwo, Osun State, Nigeria (Recruiting)
• University College Hospital — Ibadan, Oyo State, Nigeria (Recruiting)
• Usman Danfodio University — Sokoto, Sokoto State, Nigeria (Recruiting)
• University of Abuja Teaching Hospital — Gwagwalada, Nigeria (Recruiting)

Study contacts

• Principal investigator: Olanisun O Adewole, MD — Obafemi Awolowo University /Teaching Hospital, Ile- Ife, Osun State, Nigeria
• Study coordinator: Olanisun O Adewole, MD

Conditions Pulmonary Tuberculosis; Tuberculosis; Koch's Disease; Atorvastatin; Anti-tuberculosis; HMG-COA Inhibitor; Statins; Anti TB drugs