Atorvastatin with standard TB medication to find the best dose for pulmonary tuberculosis

Population Pharmacokinetics and Pharmacodynamics of Standard First Line Anti-TB Versus Atorvastatin-Containing Regimens in the Treatment of Pulmonary Tuberculosis: A Sub-study of the ATORTUB Phase 2C Randomized Controlled Trial (ATORTUB popPK-PD Study)

This trial tests whether adding different daily doses of atorvastatin to standard treatment helps adults with drug-sensitive pulmonary tuberculosis.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: Obafemi Awolowo University Teaching Hospital (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 3 sites (Zaria, Kaduna State and 2 other locations)
• Trial ID: NCT07303699 on ClinicalTrials.gov

What this trial studies

This is a randomized, parallel, dose-comparison pharmacokinetic–pharmacodynamic sub-study embedded in the ATORTUB program that enrolls adults with sputum-positive, drug-sensitive pulmonary TB. Participants are randomized into four arms (three different atorvastatin doses plus the standard fixed-dose anti-TB combination) and receive standard anti-TB therapy for 24 weeks while atorvastatin is given daily during the first 16 weeks in the experimental arms. The study collects sparse PK samples, PD measures, sputum specimens, chest x-rays, and lung function tests at scheduled visits and follows participants for a total of 52 weeks post-randomization. PK/PD modeling of atorvastatin concentrations and pharmacodynamic responses will be used to identify an optimal adjunctive dose for future TB trials.

Who should consider this trial

Good fit: Ideal participants are people aged 12 and older with sputum-positive, drug-sensitive pulmonary TB who have had little or no prior anti-TB treatment, meet baseline lab criteria, agree to HIV testing, and can attend regular clinic visits at the study sites in Nigeria.

Not a fit: People with drug-resistant TB, significant baseline liver or kidney abnormalities, extensive prior anti-TB therapy, younger than 12 years, or who cannot commit to follow-up visits are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, the study could identify an atorvastatin dose that improves treatment response when given alongside standard therapy for pulmonary TB.

How similar studies have performed: Preclinical research and small early-phase human studies have suggested statins may have beneficial host-directed effects in TB, but clinical evidence for atorvastatin as an adjunctive TB treatment remains limited.

Eligibility criteria

Inclusion Criteria:

* Sputum specimen positive for tubercle bacilli on Gene Xpert or direct smear microscopy
* Either no previous anti-TB chemotherapy, or less than 2 weeks of previous chemotherapy
* Aged 12years and above
* A firm home address that is readily accessible for visiting
* Agreement to participate in the study and to give a sample of blood for HIV testing
* Normal baseline laboratory values 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
* Informed consent to participate in the study and to give a sample of blood for HIV testing

Exclusion Criteria:

* Participants known or suspected of having any form of drug resistance TB.
* Patients co infected with HIV
* Those with poor general condition where no delay in treatment can be tolerated
* 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.
* Known or family history of bleeding disorders.
* Any renal impairment characterized by serum creatinine clearance of 1.5 x upper limit of normal of the clinical laboratory reference range at screening.
* Myositis and or Creatinine phosphokinase three times upper limit of normal
* Patient in a moribund state
* Has TB meningitis
* Presence of any of the pre-existing non-TB diseases outlined in the protocol
* Diabetes mellitus
* Hypertension
* Currently on anti TB medication
* Any other chronic illness/ co morbidities that warrants being on daily routine medications
* Presence of a psychiatric illness
* pregnant, or breast feeding mothers
* Current Tobacco Smokers/ tobacco use in any form
* Alcoholism
* alcoholic beverages, food or drinks containing methyl- xanthine (i.e. energy drinks, tea leaves, coffee beans, cocoa, kola nuts, medications e.g. theophylline). Ingestion of grapefruit/ products containing grapefruit juice, bitter oranges, garlic supplements, St John's Wort or other herbal supplements, within 7 days prior to the first treatment and throughout the study will not be allowed.
* Individuals that are enrolled in other therapeutic clinical trials

Where this trial is running

Zaria, Kaduna State and 2 other locations

• National Tuberculosis and Leprosy Training Centre, Saye — Zaria, Kaduna State, Nigeria (Recruiting)
• Federal Teaching Hospital — Katsina, Katsina State, Nigeria (Recruiting)
• Obafemi Awolowo University Teaching Hospitals Complex, Ile Ife, Osun state, Nigeria — Ile-Ife, Osun State, Nigeria (Recruiting)

Study contacts

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

Conditions Pulmonary Tuberculosis; Pulmonary TB; Tuberculosis; Koch' s disease; Mycobacterium tuberculosis; Isoniazid; Atorvastatin