Treating Tuberculosis With the Lipid Lowering Drug Atorvastatin in Nigeria(ATORvastatin in Pulmonary TUBerculosis)

NCT04721795 | Completed Phase 2 DMC

• 2 other identifiers: ERC/2020/10/05NHREC/27/02/2009a
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 2

Brief Summary

Tuberculosis (TB) is caused by mycobacterial organism. It is the leading infectious disease cause of death globally, with more than 10 million new cases and over 2 million deaths annually. Developing countries bear the greatest brunt of the disease. The long duration of current treatment is associated with poor compliance, thereby contributing to frequent relapses and to the emergence of drug-resistant TB. In addition, individuals who have been clinically cured may have lung damage, which could be permanent. Therefore, new and more effective therapeutic agents against TB are needed. Emerging evidence has shown that lipid lowering drugs like statins can make the TB bacteria more susceptible to current treatments. This proof-of-concept clinical trial will add the repurposed drug atorvastatin, commonly used to reduce cholesterol levels, to the standard therapies of TB patients in Nigeria. Atorvastatin is a well-tolerated and safe drug, and its addition is expected to accelerate clearance of the TB-causing bacteria without additional side effects. If this research is successful, it could provide evidence for using a common, easily available generic drug to improve treatment of one of the most debilitating infectious diseases.

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Keywords

lipids drugs; atorvastatin; outcome

Outcome Measures

Primary Outcomes (4)

• Primary outcome measures Efficacy of atorvastatin treatment in combination with standard anti-TB chemotherapy

  Sputum conversion at 2 month as measured by the number of patients with a negative culture

  2 months

• Time to sputum conversion

  Time to sputum conversion as measured by the time interval to the first sputum negative result with sputum smear microscopy/GenXpert

  up to 2months

• Early Bactericidal Activity

  Overall response rate associated with atorvastatin treatment in combination Measured as the Daily Rate of Change in log10 Colony Forming Units of M. Tuberculosis in Sputum on Solid Media Overall response rate associated with atorvastatin treatment in combination with standard anti-TB chemotherapy

  up to 2 weeks

• Incidence of treatment-emergent adverse events

  Incidence of treatment-emergent adverse events associated with atorvastatin treatment in combination with standard anti TB chemotherapy.

  Up till 2months

Secondary Outcomes (1)

• Plasma level of atorvastatin in combination with standard anti TB chemotherapy

  Up to 2months

Other Outcomes (1)

• Exploratory Outcome measure

  up to 2months

Study Arms (2)

Atorvastatin with standard anti tuberculosis drugs

EXPERIMENTAL

Participants will receive oral 30/40mg of atorvastatin daily for 2 months together with oral doses of standard antituberculosis drugs consisting of Rifampicin, INH, Ethambuthol and pyrazinamide for 2months. At the end of 2months, participants will continue with only standard anti tuberculosis drugs, Rifampicin and INH for 4months.Doseage of antituberculosis drugs are dependent on weight

Drug: Atorvastatin with standard anti tuberculosis drugs

Anti tuberculosis drugs only

ACTIVE COMPARATOR

Participants will receive oral doses of standard antituberculosis drugs only consisting of Rifampicin, INH, Ethambuthol and pyrazinamide for 2months. At the end of 2months, participants will continue with only standard anti tuberculosis drugs, Rifampicin and INH for 4months.Doseage of antituberculosis drugs are dependent on weight

Drug: Standard anti tuberculosis drugs only

Interventions

Atorvastatin with standard anti tuberculosis drugs DRUG

Participants will receive oral 30/40mg of atorvastatin daily for 2 months together with oral doses of standard antituberculosis drugs consisting of Rifampicin, INH, Ethambuthol and pyrazinamide for 2months. At the end of 2months, participants will continue with only standard anti tuberculosis drugs, Rifampicin and INH for 4months.Doseage of antituberculosis drugs are dependent on weight

Also known as: Atorvastatin, Statins

Atorvastatin with standard anti tuberculosis drugs

Standard anti tuberculosis drugs only DRUG

Participants will receive oral doses of standard antituberculosis drugs consisting of Rifampicin, INH, Ethambuthol and pyrazinamide for 2months. At the end of 2months, participants will continue with only standard anti tuberculosis drugs, Rifampicin and INH for 4months.Doseage of antituberculosis drugs are dependent on weight

Also known as: Rifampicin, INH, Ethambuthol and Pyrazinamide

Anti tuberculosis drugs only

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed, uncomplicated, drug-susceptible pulmonary TB
• Sputum Smear, culture or GenXpert result positive for pulmonary TB
• Ability to provide written, informed consent prior to trial initiation
• Male or and non pregnant female participants between 18 and 65 years of age
• Body mass index 16.0 and 32.0 kg/m2
• Ability to produce an adequate volume of sputum (approximately 10 -15mL or more estimated overnight production).

You may not qualify if:

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• 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

Sponsors & Collaborators

• Obafemi Awolowo University Teaching Hospital: lead
• University Hospital Birmingham NHS Foundation Trust: collaborator
• Cures Within Reach: collaborator

Study Sites (2)

Obafemi Awolowo University Teaching Hospitals Complex

Ile-Ife, Osun State, Nigeria

Location

Birmingham Heartlands Hospital

Birmingham, United Kingdom

Location

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Tuberculosis

Interventions

Atorvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rifampin; Isoniazid; Pyrazinamide

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; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Pyrazines

Study Officials

• Olanisun P Adewole, MD

  Obafemi Awolowo University Teaching Hospitals Complex

  PRINCIPAL INVESTIGATOR

• Bolanle A Omotoso, MD

  Obafemi Awolowo University Teaching Hospitals Complex

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome assesor is blinded to treatment groups
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator/Consultant Physician and Professor of Medicine

Model Details: Randomised

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: January 25, 2021
• Study Start: January 19, 2021
• Primary Completion: March 31, 2022
• Study Completion: June 30, 2022
• Last Updated: December 8, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

NG (1); GB (1)