TuberculosisPhase 2NCT03882177
StAT-TB (Statin Adjunctive Therapy for TB): A Phase 2b Dose-finding Study of Pravastatin in Adults With Tuberculosis
A Phase 2 study testing Pravastatin, Rifafour and Vitamin B6 in people with Tuberculosis and Pulmonary Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in South Africa.
Trial summary
The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of pravastatin adjunctive therapy when combined with the standard tuberculosis (TB) treatment regimen in adults with TB. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, Pulmonary Tuberculosis
- What is being tested?
- Pravastatin, Rifafour and Vitamin B6
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteSouth Africa
- Study dates
- 21 Feb 2020to 31 Dec 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 MTB/RIF with a cycle threshold (Ct) less than 28.
- Documentation of HIV status
- Weight greater than or equal to 45 kg
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- Karnofsky score of at least 60
- Ability to provide informed consent
- Ability to adhere to study follow-up visits
- Negative pregnancy test in women of child-bearing age
- Ability to adhere to contraceptive requirements and willing to use two forms of contraception: 1) a double barrier method to prevent pregnancy (i.e. use of a condom with either diaphragm or cervical cap) or 2) use of an intrauterine device in combination with a barrier contraceptive. The participant must be willing to continue these contraceptive measures throughout the duration of the study and until one week after the last dose of study medication or one week after discontinuation from study medication in case of premature discontinuation.
- Five days or fewer of anti-tuberculosis treatment within the previous 3 months
Who cannot join
- 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 CD4+ T-cell count less than 350/mm^3
Show all 27Show fewer
- Use of antiretroviral drugs
- Hemoglobin concentration less than 8 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 2.5 times the upper limit of normal (Grade 1)
- 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 less than 100,000/mm^3
- Absolute neutrophil count (ANC) less than 1,000/mm^3
- Pregnant or breastfeeding;
- Silico-tuberculosis.
- Currently receiving TB treatment
- Serologies or PCR positive for viral hepatitis (Hepatitis, B, C)
- Concomitant disorders or conditions for which isoniazid, rifampin, pyrazinamide, or ethambutol is contraindicated. These include cirrhosis, 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 determined to be resistant to rifampin by GeneXpert.
- 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
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of pravastatin adjunctive therapy when combined with the standard tuberculosis (TB) treatment regimen in adults with TB.
Read the detailed description
This study will assess the safety, tolerability, and pharmacokinetics of pravastatin adjunctive therapy when combined with the standard TB treatment regimen in adults with drug-sensitive TB. The pharmacokinetic data for pravastatin will be used to choose a dose to be studied as adjunctive TB treatment in subsequent trials.
This study is a dose-escalation trial, and participants will be sequentially enrolled into four study arms. Participants will receive standard anti-TB therapy (Rifafour) and pravastatin daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15.
Total study duration for participants will be 30 days, during which time participants will attend several study visits. Study visits may include sputum specimen collection, blood and urine collection, lung function testing, and pharmacokinetic assessments. All study participants will be referred appropriately to continue standard TB treatment at study completion.
- Conditions
- Tuberculosis, Pulmonary Tuberculosis
- Being tested
- Pravastatin, Rifafour, Vitamin B6
- Medical subject headings
- Tuberculosis, Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PravastatinDrug
Tablets, administered orally
RifafourDrug
Fixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally
Vitamin B6Dietary supplement
Administered orally.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Pravastatin (40 mg) and Rifafour | Experimental | Participants will receive pravastatin (40 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15.
Vitamin B6 will be added to each of the regimens. Receives: Drug: Pravastatin; Drug: Rifafour; Dietary Supplement: Vitamin B6 |
| Arm 2: Pravastatin (80 mg) and Rifafour | Experimental | Participants will receive pravastatin (80 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15.
Vitamin B6 will be added to each of the regimens. Receives: Drug: Pravastatin; Drug: Rifafour; Dietary Supplement: Vitamin B6 |
| Arm 3: Pravastatin (120 mg) and Rifafour | Experimental | Participants will receive pravastatin (120 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15.
Vitamin B6 will be added to each of the regimens.
(Arm 3 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.) Receives: Drug: Pravastatin; Drug: Rifafour; Dietary Supplement: Vitamin B6 |
| Arm 4: Pravastatin (160 mg) and Rifafour | Experimental | Participants will receive pravastatin (160 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15.
Vitamin B6 will be added to each of the regimens.
(Arm 4 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.) Receives: Drug: Pravastatin; Drug: Rifafour; Dietary Supplement: Vitamin B6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Grade 3 or Higher Adverse Events
Graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
Measured: Measured through Day 30
Secondary outcomes (1)
Number of Participants Who Permanently Discontinue Assigned Study Regimen for Any Reason
(Other than new recognition of participant ineligibility based on absence of M. tuberculosis growth in baseline sputum cultures, or growth of M. tuberculosis resistant to rifampin by GeneXpert)
Measured: Measured through Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2019
- Study start21 Feb 2020
- Primary completion12 May 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Petros C. Karakousis, MD, Principal investigator, Johns Hopkins UniversityRichard E. Chaisson, MD, Principal investigator, Johns Hopkins UniversityNeil Martinson, MD, MPH, Principal investigator, University of Witwatersrand, South Africa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03882177
- Sponsor's protocol ID
- StAT-TB
- Other IDs
- 38558
- Status last verified
- Aug 2023
- First submitted
- 18 Mar 2019
- Last updated
- 18 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- StAT-TB (Statin Adjunctive Therapy for TB): A Phase 2b Dose-finding Study of Pravastatin in Adults With Tuberculosis
- ClinicalTrials.gov ID
- NCT03882177
- Acronym / sponsor ID
- StAT-TB
- Conditions
- Tuberculosis, Pulmonary Tuberculosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 21 Feb 2020 (actual)
- Primary completion
- 12 May 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 20 Mar 2019 (actual)
- Results
- Posted 18 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of pravastatin adjunctive therapy when combined with the standard tuberculosis (TB) treatment regimen in adults with TB.
Detailed description
This study will assess the safety, tolerability, and pharmacokinetics of pravastatin adjunctive therapy when combined with the standard TB treatment regimen in adults with drug-sensitive TB. The pharmacokinetic data for pravastatin will be used to choose a dose to be studied as adjunctive TB treatment in subsequent trials.
This study is a dose-escalation trial, and participants will be sequentially enrolled into four study arms. Participants will receive standard anti-TB therapy (Rifafour) and pravastatin daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15.
Total study duration for participants will be 30 days, during which time participants will attend several study visits. Study visits may include sputum specimen collection, blood and urine collection, lung function testing, and pharmacokinetic assessments. All study participants will be referred appropriately to continue standard TB treatment at study completion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Pravastatin (40 mg) and Rifafour | Experimental | Drug: Pravastatin, Drug: Rifafour, Dietary Supplement: Vitamin B6Participants will receive pravastatin (40 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. |
| Arm 2: Pravastatin (80 mg) and Rifafour | Experimental | Drug: Pravastatin, Drug: Rifafour, Dietary Supplement: Vitamin B6Participants will receive pravastatin (80 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. |
| Arm 3: Pravastatin (120 mg) and Rifafour | Experimental | Drug: Pravastatin, Drug: Rifafour, Dietary Supplement: Vitamin B6Participants will receive pravastatin (120 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. (Arm 3 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.) |
| Arm 4: Pravastatin (160 mg) and Rifafour | Experimental | Drug: Pravastatin, Drug: Rifafour, Dietary Supplement: Vitamin B6Participants will receive pravastatin (160 mg) and Rifafour daily for 14 days. Pravastatin will be given alone on Day 1, and pravastatin + Rifafour will be given on Days 2-15. Vitamin B6 will be added to each of the regimens. (Arm 4 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.) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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 MTB/RIF with a cycle threshold (Ct) less than 28.
- Documentation of HIV status
Key exclusion criteria (27 listed)
- 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:
- For HIV-positive individuals, a CD4+ T-cell count less than 350/mm^3
- Use of antiretroviral drugs
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PravastatinTablets, administered orally | Drug | Arm 1: Pravastatin (40 mg) and Rifafour, Arm 2: Pravastatin (80 mg) and Rifafour, Arm 3: Pravastatin (120 mg) and Rifafour, Arm 4: Pravastatin (160 mg) and Rifafour |
| RifafourFixed-dose combination (isoniazid, rifampin, pyrazinamide, and ethambutol) tablets, administered orally | Drug | Arm 1: Pravastatin (40 mg) and Rifafour, Arm 2: Pravastatin (80 mg) and Rifafour, Arm 3: Pravastatin (120 mg) and Rifafour, Arm 4: Pravastatin (160 mg) and Rifafour |
| Vitamin B6Administered orally. | Dietary supplement | Arm 1: Pravastatin (40 mg) and Rifafour, Arm 2: Pravastatin (80 mg) and Rifafour, Arm 3: Pravastatin (120 mg) and Rifafour, Arm 4: Pravastatin (160 mg) and Rifafour |
Primary outcome
Frequency of Grade 3 or Higher Adverse Events
Time frame: Measured through Day 30
Graded using the DAIDS table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017
1 secondary outcome
Number of Participants Who Permanently Discontinue Assigned Study Regimen for Any Reason
Time frame: Measured through Day 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Petros C. Karakousis, MD principal investigator
Johns Hopkins University
Richard E. Chaisson, MD principal investigator
Johns Hopkins University
Neil Martinson, MD, MPH principal investigator
University of Witwatersrand, South Africa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pravastatin, Rifafour and Vitamin B6 in people with Tuberculosis and Pulmonary Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of Grade 3 or Higher Adverse Events (time frame: Measured through Day 30). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2023.