ATORvastatin in Pulmonary TUBerculosis

NCT06199921 | Recruiting Phase 2 DMC

• 2 other identifiers: ERC/2023/11/15IRB/IEC/0004553
• Study Type: interventional
• Target: 440
• Locations: 1 country
• Sites: 8

Brief Summary

Tuberculosis (TB) is caused by mycobacterial organism. It is the leading infectious disease cause of death globally. According to recent estimates from the World Health Organization (WHO), over 10 million new cases and 1.6 million deaths from TB occurred in 2021. The vast majority of TB cases and TB deaths are in developing countries. Nigeria has the highest TB burden in Africa with a high number of undetected TB cases as well. The spread of HIV has fueled the TB epidemic, and TB is the leading cause of death among patients infected with HIV and has assumed the lead position as the number one infectious disease cause of death globally. Even though the COVID-19 was associated with a huge mortality, TB contributed significantly to death and one of the single predictors of death among COVID-19 infected individuals. TB predominantly affects young adults in their most productive years of life and has substantial impact on economic development. Emerging evidence has shown that lipid lowering drugs like statins can make the TB bacteria more susceptible to current treatment regimen. The ATORTUB group recently completed Phase II A and Phase IIB studies to assess the safety, tolerability and efficacy of atorvastatin when administered with the current standard of care. The investigators demonstrated that atorvastatin is well tolerated, save, and has beneficial microbiological and radiological impacts in tuberculosis, thus, warrants further studies. This phase IIC trial sets out to evaluate the safety and efficacy of different doses of atorvastatin containing regimen, determine rate of decline of viable sputum bacilli, the time to stable sputum conversion, improvement in chest ray severity scores and lung function parameters post randomization in the different treatment arms. The phase II C is a Selection Trial with Extended follow-up STEP and has been devised as a pilot phase III where patients are studied for longer period (12months post randomization) than the usual phase IIB. Thus, providing additional data that will justify a successful phase III trial.

Conditions

Pulmonary Tuberculosis; Tuberculosis; Koch's Disease

Keywords

Atorvastatin; Anti-tuberculosis; HMG-COA Inhibitor; Statins; Anti TB drugs

Outcome Measures

Primary Outcomes (4)

• Safety: Proportion of participants with grade 3 or higher adverse events during study drug treatment

  Proportion of participants with grade 3 or higher adverse effect as measured by (CTCAE) v5.0

  for 24 weeks post randomization

• Efficacy: TB disease-free survival at six months post randomization

  The proportion of participants with TB disease-free survival post randomization * They have negative sputum culture. * if at the end of the follow-up period, they are clinically without symptoms/signs of ongoing active TB and are unable to produce a sputum specimen * If at the end of the follow-up period they are clinically without symptoms/signs of ongoing active TB and produce a sputum without evidence of M. tuberculosis * if at the end of the follow-up period, they have at least 30% improvement in chest severity score and 15% improvement in spirometric values.

  six months post randomization

• Efficacy:Time to stable sputum culture conversion on solid and /liquid media

  Time to achieve culture negative sputum result as measured by growth on solid mycobacteria culture medum

  up to 24 weeks post randomization

• Efficacy: Proportion of participants who are culture negative

  Proportion of participants who have Sputum culture negative specimens at the end of treatment

  Up till 24 weeks post randomization.

Secondary Outcomes (4)

• Efficacy: TB disease-free survival at twelve months post randomization

  52 weeks post randomization

• Efficacy: Proportion of participants who are symptom free at 12 months post randomization

  52 weeks post randomization

• Efficacy: Proportion of participants with improved chest x-ray severity

  52 weeks post randomization

• Efficacy: Proportion of participants with improvement in lung function post treatment

  Up till 52 weeks post randomization.

Other Outcomes (1)

• Diagnostic utility of Sweat TB test

  At enrolment

Study Arms (4)

20mg atorvastatin with standard of care (SOC) for TB

EXPERIMENTAL

Trial of 20mg atorvastatin with standard of care (SOC) for TB

Drug: Atorvastatin 20mg

40mg atorvastatin with standard of care (SOC) for TB

EXPERIMENTAL

Trial of 40mg atorvastatin with standard of care (SOC) for TB

Drug: Atorvastatin 40mg

60mg atorvastatin with standard of care (SOC) for TB

EXPERIMENTAL

Trial of 60mg atorvastatin with standard of care (SOC) for TB

Drug: Atorvastatin 60mg

Standard of care (SOC) for TB

ACTIVE COMPARATOR

Standard of care (SOC) for TB

Drug: Fixed dose combination of Rifampicin (R) Isoniazid (H) Pyrazinamide (Z) Ethambutol (E)

Interventions

Atorvastatin 20mg DRUG

Participants will receive oral atorvastatin 20mg daily for 16 weeks

Also known as: Astin

20mg atorvastatin with standard of care (SOC) for TB

Atorvastatin 40mg DRUG

Participants will receive oral atorvastatin 40mg daily for 16 weeks

Also known as: Astin

40mg atorvastatin with standard of care (SOC) for TB

Atorvastatin 60mg DRUG

Participants will receive oral atorvastatin 60 mg daily for 16 weeks

Also known as: Astin

60mg atorvastatin with standard of care (SOC) for TB

Fixed dose combination of Rifampicin (R) Isoniazid (H) Pyrazinamide (Z) Ethambutol (E) DRUG

Participants will receive 8 weeks of daily oral treatment with rifampin, isoniazid, pyrazinamide, ethambutol, followed by 16 weeks of daily oral treatment with rifampin, isoniazid

Standard of care (SOC) for TB

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Obafemi Awolowo University Teaching Hospital: lead
• Open Philanthropy: collaborator

Study Sites (8)

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, 2345, 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

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Interventions

Atorvastatin; Isoniazid; Protons; Pyrazinamide; Ethambutol

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)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Cations, Monovalent; Cations; Ions; Electrolytes; Inorganic Chemicals; Hydrogen; Elements; Gases; Nucleons; Elementary Particles; Physical Phenomena; Pyrazines; Ethylenediamines; Diamines; Polyamines; Amines

Study Officials

• Olanisun O Adewole, MD

  Obafemi Awolowo University /Teaching Hospital, Ile- Ife, Osun State, Nigeria

  PRINCIPAL INVESTIGATOR

• Olanisun O Adewole, MD

  Obafemi Awolowo University/ Teaching Hospital, Ile- Ife, Osun State, Nigeria

  STUDY CHAIR

• Bolanle A Omotoso, MD

  Obafemi Awolowo University/ Teaching Hospital, Ile- Ife, Osun State, Nigeria

  STUDY DIRECTOR

Central Study Contacts

Olanisun O Adewole, MD

CONTACT

+2348034074930; adewolef@yahoo.co.uk , ola.adewole@oauife.edu.ng

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 3, 2023
• First Posted: January 10, 2024
• Study Start: January 3, 2024
• Primary Completion: March 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NG (8)