Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT04504851
Other study ID # ROSETTA
Secondary ID
Status Not yet recruiting
Phase Phase 2
First received
Last updated
Start date August 12, 2020
Est. completion date March 31, 2021

Study information

Verified date August 2020
Source National University Hospital, Singapore
Contact Gail Cross
Phone +65 83280377
Email mdcgbc@nus.edu.sg
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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.


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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 154
Est. completion date March 31, 2021
Est. primary completion date March 31, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility Inclusion Criteria:

1. Aged 18 - 75 years of age

2. Abnormalities on CXR compatible with pulmonary TB

3. At least one sputum specimen, produced at or prior to screening during the current illness episode, that is:

(i) 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')

4. Able to produce at least 5ml of sputum per day at the time of screening

5. Current or planned treatment with a regimen containing rifampicin, isoniazid and pyrazinamide (with or without ethambutol) only

6. 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

7. Willing to have directly observed therapy (DOT)

8. Willing to comply with the study visits and procedures

Exclusion Criteria:

1. More than 7 days of standard TB treatment by the time of the baseline visit

2. 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)

3. Previous treatment for active TB disease, unless rifampicin susceptibility has been demonstrated on a molecular test performed during this episode.

4. Extrapulmonary TB that, in the opinion of the treating clinician, is likely to require concurrent use of steroids, or require surgical management.

5. Known hypersensitivity to rosuvastatin

6. History of myopathy or family history of hereditary muscular disorders

7. Acute liver failure or decompensated chronic liver disease

8. Current alcohol abuse

9. Known hypothyroidism

10. Any of the following laboratory parameters at screening:

1. ALT >3 times upper limit of normal (ULN)

2. Estimated glomerular filtration rate (eGFR) < 60ml/min/1.73m2 (calculated using the CKD-EPI equation) (81)

3. Creatine Kinase >5 times ULN

4. Potassium <2.5 mmol/L

11. Active malignancy on chemotherapy or radiotherapy

12. Current use of immunosuppressive medication (= 5mg/ day of prednisolone or equivalent is acceptable).

13. 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)

14. Use of any statin drug at screening or during the 3 months prior to screening

15. 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)

16. Known Familial Hypercholesterolaemia

17. 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

18. 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.

19. Women who are pregnant or breastfeeding

20. Women of childbearing potential unwilling or unable to use appropriate effective contraception for the first 12 weeks of the trial.

21. 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)

22. Any other severe underlying condition that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial.

23. 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).

Study Design


Intervention

Drug:
Rosuvastatin 10mg
10mg of Rosuvastatin in the Intensive Phase of Therapy (8 weeks)
Rifampicin
Rifampicin 10mg/kg
Isoniazid
Isoniazid 5mg/kg
Pyrazinamide
Pyrazinamide 25mg/kg
Ethambutol
Ethambutol 15mg/kg

Locations

Country Name City State
Philippines Tropical Disease Foundation Makati City
Philippines De La Salle Health Sciences Institute Manila
Philippines Lung Center Philippines Quezon City
Singapore National University Hospital, Singapore Singapore
Uganda Joint Clinical Research Centre Kampala
Vietnam Vietnam Military Medical University Hanoi

Sponsors (1)

Lead Sponsor Collaborator
National University Hospital, Singapore

Countries where clinical trial is conducted

Philippines,  Singapore,  Uganda,  Vietnam, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 within 8 weeks after randomisation
Secondary 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 within 8 weeks after randomisation
Secondary 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 within 12 weeks after randomisation
Secondary Sputum culture negative in Liquid media at 8 weeks from randomisation
Secondary Sputum culture negative in Solid media at 8 weeks from randomisation
Secondary Change in time to positivity (TTP) from baseline to week 8
Secondary Change in proportion of lung affected on CXR from baseline to week 8
Secondary Change in the aggregate cavity size on CXR from baseline to week 8
Secondary Change in score on St George's Respiratory Questionnaire (SGRQ) from baseline to week 8
Secondary Change in FEV1/FVC from baseline to week 8
Secondary One or more Grade 3 or Grade 4 adverse events by week 24
Secondary One of more Serious Adverse Events (SAEs) by week 24
See also
  Status Clinical Trial Phase
Completed NCT02736864 - Structural and Functional Repercussions of Pulmonary Tuberculosis Sequelae N/A
Not yet recruiting NCT04055441 - A Study of Pattern of Presentation of Pulmonary Tuberculosis Patients Undergoing Treatment at Assiut University Hospital
Completed NCT02349841 - Phase 2 Trial to Evaluate the Early Bactericidal Activity, Safety and Tolerability of Meropenem Plus Amoxycillin/CA and Faropenem Plus Amoxycillin/CA in Adult Patients With Newly Diagnosed Pulmonary Tuberculosis Phase 2
Completed NCT01927159 - Phase 1 ID93 + GLA-SE Vaccine Trial in BCG-Vaccinated Healthy Adult Volunteers Phase 1
Active, not recruiting NCT01691534 - Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With Clofazimine (C)-TMC207 (J)-PA-824 (Pa)-Pyrazinamide (Z) Phase 2
Completed NCT00803322 - Improving Community Based Tuberculosis Care in Ethiopia Phase 4
Completed NCT00834353 - Prospective Study of N-acetyltransferase2 (NAT2) and Cytochrome P4502E1 (CYP2E1) Gene as Susceptible Risk Factors for Antituberculosis (ATT) Induced Hepatitis N/A
Withdrawn NCT03277742 - Joint Management of DM2 and Pulmonary TB in Orizaba, Veracruz N/A
Completed NCT00057434 - Vitamin A Therapy for Tuberculosis Phase 3
Not yet recruiting NCT06192160 - Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis Phase 2
Recruiting NCT06127641 - Rehabilitation of People With Post-tuberculosis Lung Disease N/A
Recruiting NCT06058299 - Phase 2 Trial Assessing TBAJ876 or Bedaquiline, With Pretomanid and Linezolid in Adults With Drug-sensitive Pulmonary Tuberculosis Phase 2
Completed NCT04550832 - PanACEA DElpazolid Dose-finding and COmbination DEvelopment (DECODE) Phase 2
Completed NCT02912832 - Prospective Assessment of TBDx Feasibility N/A
Completed NCT01215851 - Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With(J-M-Pa-Z) Phase 2
Recruiting NCT01503099 - Intestinal Tuberculosis Diagnostics and the Differentiation From Crohn's Disease N/A
Completed NCT04608955 - Evaluation of Early Bactericidal Activity and Safety in Pulmonary Tuberculosis With WX-081 Phase 2
Recruiting NCT05046366 - Development of an Artificial Intelligence System for Intelligent Pathological Diagnosis and Therapeutic Effect Prediction Based on Multimodal Data Fusion of Common Tumors and Major Infectious Diseases in the Respiratory System Using Deep Learning Technology.
Completed NCT05896930 - Study to Evaluate EBA, Safety and Tolerability of Carbapenems in Adults With Pulmonary Tuberculosis Phase 2
Completed NCT02279875 - A Phase 2 Trial to Evaluate the Efficacy and Safety of Linezolid in Tuberculosis Patients. (LIN-CL001) Phase 2