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Statin Adjunctive Therapy for TB (StAT- TB)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03456102
Recruitment Status : Completed
First Posted : March 7, 2018
Last Update Posted : September 27, 2022
Sponsor:
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:

There is an urgent need for novel therapies to shorten TB treatment and improve long-term lung function outcomes. Host-directed therapies (HDT) have received significant attention recently given the ability of M. tuberculosis to subvert host immune responses and cause destructive lung pathology. Statins are among the most promising HDT agents for TB. In addition to having a highly favorable safety profile, statins have been shown to have anti-TB activity in macrophages, to synergize with anti-TB drugs, and to shorten the duration of TB treatment in the standard mouse model.

The StAT-TB trial will comprise two different stages. In the 14-day Stage 1 study, investigators will test the safety and tolerability, as well as Pharmacokinetics (PK), of two different doses of pravastatin co-administered with standard anti-TB treatment. In Stage 2, investigators will test the ability of pravastatin adjunctive therapy (dose to be determined in Stage 1) to shorten the mean time to sputum culture conversion (primary endpoint) and improve lung function outcomes (secondary endpoints) relative to the standard regimen. In addition, investigators will continue to investigate the anti-TB mechanism of action of pravastatin in order to further improve HDT options for TB in the future.


Condition or disease Intervention/treatment Phase
Tuberculosis Drug: Pravastatin Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Statin Adjunctive Therapy for TB (StAT- TB)
Actual Study Start Date : March 9, 2020
Actual Primary Completion Date : August 31, 2022
Actual Study Completion Date : August 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Pravastatin 80 mg
Pravastatin 80 mg, isoniazid 300 mg, rifampin 450 mg (weight <50 kg) or 600 mg (weight >50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 2 will only be recruited if pravastatin 80 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Drug: Pravastatin

Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.

A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.


Pravastatin 120 mg
Pravastatin 120 mg, isoniazid 300 mg, rifampin 450 mg (weight <50 kg) or 600 mg (weight >50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 3 will only be recruited if pravastatin 120 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.
Drug: Pravastatin

Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.

A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.


Pravastatin 160 mg
Pravastatin 160 mg, isoniazid 300 mg, rifampin 450 mg (weight <50 kg) or 600 mg (weight >50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days
Drug: Pravastatin

Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.

A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.


Pravastatin 40 mg
Pravastatin 40 mg, isoniazid 300 mg, rifampin 450 mg (weight <50 kg) or 600 mg (weight >50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 4 will only be recruited if pravastatin 80 mg is not tolerated as specified in protocol.
Drug: Pravastatin

Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.

A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.





Primary Outcome Measures :
  1. Safety of escalating doses of pravastatin [ Time Frame: Up to 14 days ]
    Safety of escalating doses of pravastatin (40 mg - 160 mg) when co-administered with rifampin, as evidenced by number of Grade 3 or higher adverse events.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years of age or older
  • Clinical signs and symptoms of pulmonary tuberculosis
  • Abnormal chest radiograph consistent with pulmonary tuberculosis
  • At least one sputum positive for M. tuberculosis by Xpert Mycobacterium tuberculosis (MTB)/resistance to rifampicin (RIF) with a cycle threshold (Ct) <28.
  • Documentation of HIV status
  • Weight ≥45 kg
  • Karnofsky score of at least 60
  • Ability to provide informed consent
  • Ability to adhere to study follow-up visits
  • Ability to adhere to contraceptive requirements and willing to use two forms of contraception.
  • Five days or fewer of anti-tuberculosis treatment within the previous 3 months

Exclusion Criteria:

  • A history of severe adverse reactions to any statin or any other study agent or contraindications to use of statins.
  • Current use of statins or other lipid-lower agents;
  • Clinical indication for statin therapy based on cardiovascular risk (Familial hypercholesterolemia, Previous history of myocardial infarction or stroke)
  • For HIV-positive individuals, a cluster of differentiation 4 (CD4+) T-cell count <100/mm3
  • Use of antiretroviral drugs
  • Hemoglobin concentration less than 7 g/dL;
  • Baseline creatinine kinase elevation more than three times the upper limit of normal
  • Abnormal baseline laboratory values (Baseline alanine aminotransferase (ALT) concentration more than three times the upper limit of normal, Serum creatinine concentration more than twice the upper limit of normal, Serum total bilirubin level greater than twice the upper limit of normal, Platelet count < 100,000/mm3, White Blood Cell (WBC) < 2500 (mcL))
  • Pregnant or breastfeeding;
  • Silico-tuberculosis.
  • Currently receiving TB treatment
  • Concomitant disorders or conditions for which isoniazid, rifampin, pyrazinamide, or ethambutol is contraindicated. These include sever hepatic damage, acute liver disease of any cause, acute uncontrolled gouty arthritis and peripheral neuropathy.
  • Any medical or psychological condition which, in the view of the study investigator, makes study participation inadvisable.
  • Infection with an isolate known to be resistant to a first -line TB drug; for example rifampin.
  • More than five days of anti-tuberculosis treatment within the previous 3 months
  • Planned or current use of cyclosporine, tacrolimus, erythromycin or colchicine
  • Central nervous system (CNS) TB
  • Extra-pulmonary TB only, not in combination with pulmonary TB
  • History of TB

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03456102


Locations
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South Africa
Chris Hani Baragwanath Hospital
Johannesburg, South Africa
Sponsors and Collaborators
Johns Hopkins University
Investigators
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Principal Investigator: Richard Chaisson Johns Hopkins University
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03456102    
Other Study ID Numbers: IRB00145353
First Posted: March 7, 2018    Key Record Dates
Last Update Posted: September 27, 2022
Last Verified: September 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
Pravastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors