Rosuvastatin Evaluation as a Tuberculosis Treatment Adjunct

NCT04504851 | Unknown Phase 2 DMC

• 1 other identifier: ROSETTA
• Study Type: interventional
• Target: 154
• Locations: 4 countries
• Sites: 6

Brief 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.

Conditions

Pulmonary Tuberculosis

Keywords

Statin; Rosuvastatin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Time to culture conversion in Solid media

  within 8 weeks after randomisation

• Time to culture conversion in Liquid media

  within 12 weeks after randomisation

• Sputum culture negative in Liquid media

  at 8 weeks from randomisation

• Sputum culture negative in Solid media

  at 8 weeks from randomisation

• Change in time to positivity (TTP)

  from baseline to week 8

Study Arms (2)

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

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

Drug: Rosuvastatin 10mg; Drug: Rifampicin; Drug: Isoniazid; Drug: Pyrazinamide; Drug: Ethambutol

Interventions

Rosuvastatin 10mg DRUG

10mg of Rosuvastatin in the Intensive Phase of Therapy (8 weeks)

Also known as: Crestor

Arm B (Standard of Care plus Rosuvastatin)

Rifampicin DRUG

Rifampicin 10mg/kg

Arm A (Standard of Care); Arm B (Standard of Care plus Rosuvastatin)

Isoniazid DRUG

Isoniazid 5mg/kg

Arm A (Standard of Care); Arm B (Standard of Care plus Rosuvastatin)

Pyrazinamide DRUG

Pyrazinamide 25mg/kg

Arm A (Standard of Care); Arm B (Standard of Care plus Rosuvastatin)

Ethambutol DRUG

Ethambutol 15mg/kg

Arm A (Standard of Care); Arm B (Standard of Care plus Rosuvastatin)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• (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')
• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (6)

Tropical Disease Foundation

Makati City, Philippines

Location

De La Salle Health Sciences Institute

Manila, Philippines

Location

Lung Center Philippines

Quezon City, Philippines

Location

National University Hospital, Singapore

Singapore, Singapore

Location

Joint Clinical Research Centre

Kampala, Uganda

Location

Vietnam Military Medical University

Hanoi, Vietnam

Location

Related Publications (2)

• 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.

  PMID: 39622823 DERIVED

• Cross 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.

  PMID: 36966799 DERIVED

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

Rosuvastatin Calcium; Rifampin; Isoniazid; Pyrazinamide; Ethambutol

Condition Hierarchy (Ancestors)

Tuberculosis; 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)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Hydrazines; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Pyrazines; Ethylenediamines; Diamines; Polyamines; Amines

Study Officials

• Nicholas Paton

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gail Cross

CONTACT

+65 83280377; mdcgbc@nus.edu.sg

Nicholas Paton

CONTACT

+65 6601 5371; mdcnijp@nus.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 7, 2020
• Study Start: August 12, 2020
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: August 7, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

VN (1); PH (3); SG (1); UG (1)