Pulmonary TuberculosisPhase 2ROSETTANCT04504851
Rosuvastatin Evaluation as a Tuberculosis Treatment Adjunct
A Phase 2 study testing Rosuvastatin 10mg, Rifampicin and Isoniazid in people with Pulmonary Tuberculosis, run by National University Hospital, Singapore at 6 sites in 4 countries.
Trial summary
This trial aims to determine whether the addition of rosuvastatin to standard TB therapy in pulmonary tuberculosis results in accelerated of sputum culture conversion. The trial will also investigate potential new biomarkers of sterilising activity and immune-modulatory activity. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Tuberculosis
- What is being tested?
- Rosuvastatin 10mg, Rifampicin and Isoniazid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 154 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 12 Aug 2020to 31 Mar 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 - 75 years of age
- Abnormalities on CXR compatible with pulmonary TB
- At least one sputum specimen, produced at or prior to screening during the current illness episode, that is:
- positive for acid-fast bacilli on smear microscopy (with at least 1+ on the IUATLD/WHO scale) and/or (ii) positive on testing by Xpert MTB/RIF or Xpert Ultra (with semi-quantitative cycle threshold (CT) result of 'medium' or 'high')
- Able to produce at least 5ml of sputum per day at the time of screening
- Current or planned treatment with a regimen containing rifampicin, isoniazid and pyrazinamide (with or without ethambutol) only
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- Resident at a fixed address within feasible travelling distance to the site and likely to remain a local resident for the duration of trial follow-up
- Willing to have directly observed therapy (DOT)
- Willing to comply with the study visits and procedures
Who cannot join
- More than 7 days of standard TB treatment by the time of the baseline visit
- Known rifampicin resistance or isoniazid resistance at the time of randomization (results by conventional DST or molecular tests are not required to be available prior to randomization)
- Previous treatment for active TB disease, unless rifampicin susceptibility has been demonstrated on a molecular test performed during this episode.
- Extrapulmonary TB that, in the opinion of the treating clinician, is likely to require concurrent use of steroids, or require surgical management.
- Known hypersensitivity to rosuvastatin
- History of myopathy or family history of hereditary muscular disorders
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- Acute liver failure or decompensated chronic liver disease
- Current alcohol abuse
- Known hypothyroidism
- Any of the following laboratory parameters at screening:
- ALT >3 times upper limit of normal (ULN)
- Estimated glomerular filtration rate (eGFR) < 60ml/min/1.73m2 (calculated using the CKD-EPI equation) (81)
- Creatine Kinase >5 times ULN
- Potassium <2.5 mmol/L
- Active malignancy on chemotherapy or radiotherapy
- Current use of immunosuppressive medication (≤ 5mg/ day of prednisolone or equivalent is acceptable).
- HIV infection (unless patient has been stable on continuous antiretroviral therapy for at least 6 months, with CD4 count >/= 250 cells/mm3 and viral load </= 200 copies/ml, on a test performed at screening or during the last 12 months prior to screening, in which case they may be enrolled)
- Use of any statin drug at screening or during the 3 months prior to screening
- History of Atherosclerotic Cardiovascular Disease (ASCVD; defined as myocardial infarction, stable or unstable angina, coronary artery disease or coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral artery disease including aortic aneurysm, all of atherosclerotic origin)
- Known Familial Hypercholesterolaemia
- Other reasons, in the opinion of the investigator (and taking into consideration current local and international guidelines for primary prevention of cardiovascular disease), why the patient should commence statin treatment during the 6-month period following randomization
- Current use of drugs contraindicated for use with rosuvastatin or standard TB drugs including fusidic acid, gemfibrozil, feno-fibrate, nicotinic acid (>1 gram/day), cyclosporine, directly acting antivirals for chronic Hepatitis C, protease inhibitors for HIV and praziquantel.
- Women who are pregnant or breastfeeding
- Women of childbearing potential unwilling or unable to use appropriate effective contraception for the first 12 weeks of the trial.
- Any serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (such as extensive surgery, significant trauma, uncontrolled seizures)
- Any other severe underlying condition that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial.
- Participation in other clinical intervention trial or research protocol (participation in other studies that do not involve an intervention may be allowed, but this must be discussed and approved by the Chief Investigator).
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
Philippines3 sites
Tropical Disease Foundation
Makati City
De La Salle Health Sciences Institute
Manila
Lung Center Philippines
Quezon City
About this study
This trial aims to determine whether the addition of rosuvastatin to standard TB therapy in pulmonary tuberculosis results in accelerated of sputum culture conversion. The trial will also investigate potential new biomarkers of sterilising activity and immune-modulatory activity.
Read the detailed description
Rosuvastatin is an HMG Co-A reductase inhibitor which may be of value as possible adjunctive agents to standard TB therapy. Cell culture assays and animal models demonstrate that statins are bactericidal against Mtb with effects that are additive to that of anti-tuberculous therapy.
This is a Phase IIb randomised, controlled, open-label, early bactericidal activity trial. We will recruit patients between the ages of 18 and 75 with newly-diagnosed smear or Xpert positive pulmonary TB, who have had no more than 7 days of TB therapy.
Patients will be randomised to take either standard TB therapy or standard TB therapy plus rosuvastatin for the first 8 weeks of their therapy. After the first 8 weeks, patients will continue standard combination TB therapy and remain in trial follow-up until week 24. The trial will collect sputum for culture on a weekly basis for the first 8 weeks of the trial, and less frequently leading up to week 24.
- Conditions
- Pulmonary Tuberculosis
- Being tested
- Rosuvastatin 10mg, Rifampicin, Isoniazid, Pyrazinamide, Ethambutol
- Keywords
- Statin, Rosuvastatin
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rosuvastatin 10mgDrug
Also called Crestor
10mg of Rosuvastatin in the Intensive Phase of Therapy (8 weeks)
RifampicinDrug
Rifampicin 10mg/kg
IsoniazidDrug
Isoniazid 5mg/kg
PyrazinamideDrug
Pyrazinamide 25mg/kg
EthambutolDrug
Ethambutol 15mg/kg
| Study group | Role | What they receive |
|---|---|---|
| Arm A (Standard of Care) | Active comparator | Standard combination treatment for pulmonary TB of 8 weeks rifampicin, isoniazid, pyrazinamide, ethambutol, then 16 weeks rifampicin, isoniazid Receives: Drug: Rifampicin; Drug: Isoniazid; Drug: Pyrazinamide; Drug: Ethambutol |
| Arm B (Standard of Care plus Rosuvastatin) | Experimental | Standard combination treatment for pulmonary TB of 8 weeks rifampicin, isoniazid, pyrazinamide, ethambutol PLUS rosuvastatin, then 16 weeks rifampicin, isoniazid Receives: Drug: Rosuvastatin 10mg; Drug: Rifampicin; Drug: Isoniazid; Drug: Pyrazinamide; Drug: Ethambutol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to culture conversion in Liquid Media
Time to culture conversion is defined is time from randomisation to the first of two consecutive negative sputum cultures
Measured: within 8 weeks after randomisation
Secondary outcomes (11)
Time to culture conversion in Solid media
Time to culture conversion is defined is time from randomisation to the first of two consecutive negative sputum cultures
Measured: within 8 weeks after randomisation
Time to culture conversion in Liquid media
Time to culture conversion is defined is time from randomisation to the first of two consecutive negative sputum cultures
Measured: within 12 weeks after randomisation
Sputum culture negative in Liquid media
Measured: at 8 weeks from randomisation
Sputum culture negative in Solid media
Measured: at 8 weeks from randomisation
Change in time to positivity (TTP)
Measured: from baseline to week 8
Change in proportion of lung affected on CXR
Measured: from baseline to week 8
Change in the aggregate cavity size on CXR
Measured: from baseline to week 8
Change in score on St George's Respiratory Questionnaire (SGRQ)
Measured: from baseline to week 8
Change in FEV1/FVC
Measured: from baseline to week 8
One or more Grade 3 or Grade 4 adverse events
Measured: by week 24
One of more Serious Adverse Events (SAEs)
Measured: by week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2020
- Study start12 Aug 2020 (estimated)
- Primary completion31 Mar 2021 (estimated)
- Study completion31 Mar 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pulmonary TuberculosisStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 154 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicholas Paton, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04504851
- Sponsor's protocol ID
- ROSETTA
- Acronym
- ROSETTA
- Status last verified
- Aug 2020
- First submitted
- 5 Aug 2020
- Last updated
- 7 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cross GB, Sari IP, Burkill SM, Yap CW, Nguyen H, Quyet D, Dalay VB, Gutierrez E, Balanag VM, Castillo RJ, Chang CC, Kelleher AD, O'Doherty J, Paton NI. PET-CT outcomes from a randomised controlled trial of rosuvastatin as an adjunct to standard tuberculosis treatment. Nat Commun. 2024 Dec 2;15(1):10475. doi: 10.1038/s41467-024-54419-3.
PubMed 39622823Cross GB, Sari IP, Kityo C, Lu Q, Pokharkar Y, Moorakonda RB, Thi HN, Do Q, Dalay VB, Gutierrez E, Balanag VM, Castillo RJ, Mugerwa H, Fanusi F, Kwan P, Chew KL, Paton NI; ROSETTA trial team. Rosuvastatin adjunctive therapy for rifampicin-susceptible pulmonary tuberculosis: a phase 2b, randomised, open-label, multicentre trial. Lancet Infect Dis. 2023 Jul;23(7):847-855. doi: 10.1016/S1473-3099(23)00067-1. Epub 2023 Mar 23.
PubMed 36966799
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rosuvastatin Evaluation as a Tuberculosis Treatment Adjunct
- ClinicalTrials.gov ID
- NCT04504851
- Acronym / sponsor ID
- ROSETTA / ROSETTA
- Conditions
- Pulmonary Tuberculosis
- Keywords
- Statin, Rosuvastatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 154 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- 12 Aug 2020 (estimated)
- Primary completion
- 31 Mar 2021 (estimated)
- Study completion
- 31 Mar 2021 (estimated)
- First posted
- 7 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial aims to determine whether the addition of rosuvastatin to standard TB therapy in pulmonary tuberculosis results in accelerated of sputum culture conversion. The trial will also investigate potential new biomarkers of sterilising activity and immune-modulatory activity.
Detailed description
Rosuvastatin is an HMG Co-A reductase inhibitor which may be of value as possible adjunctive agents to standard TB therapy. Cell culture assays and animal models demonstrate that statins are bactericidal against Mtb with effects that are additive to that of anti-tuberculous therapy.
This is a Phase IIb randomised, controlled, open-label, early bactericidal activity trial. We will recruit patients between the ages of 18 and 75 with newly-diagnosed smear or Xpert positive pulmonary TB, who have had no more than 7 days of TB therapy.
Patients will be randomised to take either standard TB therapy or standard TB therapy plus rosuvastatin for the first 8 weeks of their therapy. After the first 8 weeks, patients will continue standard combination TB therapy and remain in trial follow-up until week 24. The trial will collect sputum for culture on a weekly basis for the first 8 weeks of the trial, and less frequently leading up to week 24.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (Standard of Care) | Active comparator | Drug: Rifampicin, Drug: Isoniazid, Drug: Pyrazinamide, Drug: EthambutolStandard combination treatment for pulmonary TB of 8 weeks rifampicin, isoniazid, pyrazinamide, ethambutol, then 16 weeks rifampicin, isoniazid |
| Arm B (Standard of Care plus Rosuvastatin) | Experimental | Drug: Rosuvastatin 10mg, Drug: Rifampicin, Drug: Isoniazid, Drug: Pyrazinamide, Drug: EthambutolStandard combination treatment for pulmonary TB of 8 weeks rifampicin, isoniazid, pyrazinamide, ethambutol PLUS rosuvastatin, then 16 weeks rifampicin, isoniazid |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Aged 18 - 75 years of age
- Abnormalities on CXR compatible with pulmonary TB
- At least one sputum specimen, produced at or prior to screening during the current illness episode, that is:
- Able to produce at least 5ml of sputum per day at the time of screening
- Current or planned treatment with a regimen containing rifampicin, isoniazid and pyrazinamide (with or without ethambutol) only
Key exclusion criteria (27 listed)
- More than 7 days of standard TB treatment by the time of the baseline visit
- Known rifampicin resistance or isoniazid resistance at the time of randomization (results by conventional DST or molecular tests are not required to be available prior to randomization)
- Previous treatment for active TB disease, unless rifampicin susceptibility has been demonstrated on a molecular test performed during this episode.
- Extrapulmonary TB that, in the opinion of the treating clinician, is likely to require concurrent use of steroids, or require surgical management.
- Known hypersensitivity to rosuvastatin
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 |
|---|---|---|
| Rosuvastatin 10mgAlso: Crestor10mg of Rosuvastatin in the Intensive Phase of Therapy (8 weeks) | Drug | Arm B (Standard of Care plus Rosuvastatin) |
| RifampicinRifampicin 10mg/kg | Drug | Arm A (Standard of Care), Arm B (Standard of Care plus Rosuvastatin) |
| IsoniazidIsoniazid 5mg/kg | Drug | Arm A (Standard of Care), Arm B (Standard of Care plus Rosuvastatin) |
| PyrazinamidePyrazinamide 25mg/kg | Drug | Arm A (Standard of Care), Arm B (Standard of Care plus Rosuvastatin) |
| EthambutolEthambutol 15mg/kg | Drug | Arm A (Standard of Care), Arm B (Standard of Care plus Rosuvastatin) |
Primary outcome
Time to culture conversion in Liquid Media
Time frame: within 8 weeks after randomisation
Time to culture conversion is defined is time from randomisation to the first of two consecutive negative sputum cultures
11 secondary outcomes
Time to culture conversion in Solid media
Time frame: within 8 weeks after randomisation
Time to culture conversion in Liquid media
Time frame: within 12 weeks after randomisation
Sputum culture negative in Liquid media
Time frame: at 8 weeks from randomisation
Sputum culture negative in Solid media
Time frame: at 8 weeks from randomisation
Change in time to positivity (TTP)
Time frame: from baseline to week 8
Change in proportion of lung affected on CXR
Time frame: from baseline to week 8
Change in the aggregate cavity size on CXR
Time frame: from baseline to week 8
Change in score on St George's Respiratory Questionnaire (SGRQ)
Time frame: from baseline to week 8
Change in FEV1/FVC
Time frame: from baseline to week 8
One or more Grade 3 or Grade 4 adverse events
Time frame: by week 24
One of more Serious Adverse Events (SAEs)
Time frame: by week 24
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2020.
- Derived from this study: PubMed 39622823Cross GB, Sari IP, Burkill SM, Yap CW, Nguyen H, Quyet D, Dalay VB, Gutierrez E, Balanag VM, Castillo RJ, Chang CC, Kelleher AD, O'Doherty J, Paton NI. PET-CT outcomes from a randomised controlled trial of rosuvastatin as an adjunct to standard tuberculosis treatment. Nat Commun. 2024 Dec 2;15(1):10475. doi: 10.1038/s41467-024-54419-3.
- Derived from this study: PubMed 36966799Cross GB, Sari IP, Kityo C, Lu Q, Pokharkar Y, Moorakonda RB, Thi HN, Do Q, Dalay VB, Gutierrez E, Balanag VM, Castillo RJ, Mugerwa H, Fanusi F, Kwan P, Chew KL, Paton NI; ROSETTA trial team. Rosuvastatin adjunctive therapy for rifampicin-susceptible pulmonary tuberculosis: a phase 2b, randomised, open-label, multicentre trial. Lancet Infect Dis. 2023 Jul;23(7):847-855. doi: 10.1016/S1473-3099(23)00067-1. Epub 2023 Mar 23.
- Individual participant dataSharing planned: No
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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.
Nicholas Paton principal investigator
National University Hospital, Singapore
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rosuvastatin 10mg, Rifampicin and Isoniazid in people with Pulmonary Tuberculosis, run by National University Hospital, Singapore at 6 sites in 4 countries.
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 9 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: status not confirmed, as of the sponsor's last update on 7 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Philippines, Singapore, Uganda, Vietnam. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gail Cross (+65 83280377, mdcgbc@nus.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to culture conversion in Liquid Media (time frame: within 8 weeks after randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04504851, which also lists 2 linked publications.
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 7 Aug 2020.