Using atorvastatin to reduce lung inflammation after tuberculosis treatment

Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Safety and Efficacy of Atorvastatin to Reduce Inflammation After Tuberculosis Treatment Completion in HIV-infected and HIV-uninfected Adults Measured by FDG-PET/CT

This study is testing if atorvastatin, a cholesterol-lowering drug, can help adults who have finished tuberculosis treatment by reducing lingering lung inflammation.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 220 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: University of Cape Town (Academic / other)
• Locations: 1 site (Observatory, WC)
• Trial ID: NCT04147286 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of atorvastatin, a cholesterol-lowering medication, in reducing persistent lung inflammation in adults who have completed treatment for tuberculosis (TB). The study is a double-blind, randomized, placebo-controlled trial that aims to determine if atorvastatin can enhance recovery by targeting inflammation and potential residual infection. Participants include both HIV-infected and uninfected adults who have shown a clinical response to TB treatment. The effectiveness will be measured using advanced imaging techniques like PET/CT to assess lung inflammation.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 who have completed a standard TB treatment course and are either HIV-infected or uninfected.

Not a fit: Patients with severe liver or kidney dysfunction, or those who do not meet the specific health criteria outlined in the eligibility criteria, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve recovery outcomes for patients who have completed TB treatment by reducing inflammation and preventing recurrence.

How similar studies have performed: Previous studies have shown that statins can reduce TB burden and improve lung health, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria

1. Has completed the written informed consent process prior to undergoing any pre-screening or screening evaluations and willing to undergo HIV testing
2. Age 18 to 65 years with body weight from 50 kg to 90 kg
3. Clinical response to TB treatment and sputum culture negative at week 16
4. Completed a 24-week course of standard TB treatment (4RHZE/2RH)
5. Defined as "cured" by the TB Control Program of South Africa

   Laboratory parameters within 30 days before enrolment:
6. For HIV-infected participants: receiving antiretroviral therapy for at least 12 weeks and suppressed HIV viral load within 30 days prior to enrolment
7. For HIV-infected participants: CD4 counts above 350 cells/µL within 30 days prior to enrolment
8. AST and ALT \<3x upper limit of normal (ULN)
9. Creatinine \<2x ULN
10. Hemoglobin \>7.0 g/dL
11. Platelet count \>50 x109 cells/L
12. Creatinine kinase \<2x ULN
13. Able and willing to return to follow-up
14. Willing to have samples, including DNA, stored
15. Willing to consistently practice a highly reliable method of pregnancy prevention

Exclusion criteria

1. Acute illness
2. Fever (temperature \>38.0 degrees centigrade)
3. Participant receiving any type of lipid lowering agent at the time of screening, within three months prior to screening or likely to require any lipid lowering agent in the near future.
4. Known allergy or contraindications to the investigational drug or any other statins
5. Evidence of drug-resistant TB
6. Extrapulmonary TB, including pleural TB and/or large pleural effusion
7. Pregnant or desiring/trying to become pregnant in the next 6 months
8. Unable to take oral medications
9. Diabetes as defined by point of care HbA1c≥6.5, random glucose≥200mg/dL (or 11.1mmol/L), fasting plasma glucose≥126mg/dL (or 7.0mmol/L), or the presence of any anti-diabetic agent (including traditional medicines) as a concomitant medicine
10. Disease complications or concomitant illnesses that may compromise safety or interpretation of trial endpoints, such as known diagnosis of chronic inflammatory condition (e.g. sarcoidosis, rheumatoid arthritis, connective tissue disorder)
11. Use of immunosuppressive medications, such as TNF-alpha inhibitors or systemic or inhaled corticosteroids, within the past 2 weeks
12. Use of any investigational drug in the previous 3 months
13. Alcohol and substance abuse which might interfere with medication adherence during the trial
14. Any person for whom the physician feels this study is not appropriate

Where this trial is running

Observatory, WC

• General Medicine & Global Health, Cape Heart Institute, Faculty of Health Sciences, University of Cape Town — Observatory, Wc, South Africa (Recruiting)

Study contacts

• Principal investigator: Friedrich Thienemann, MD — University of Cape Town
• Study coordinator: Friedrich Thienemann, MD

Conditions Tuberculosis, Pulmonary; tuberculosis; HIV; COPD; inflammation