Drug Exposure and Safety of a Shorter Tuberculosis Treatment Based on High-Dose Rifampicin and Pyrazinamide

• Status: Recruiting
• Trial end date: 2026-05-31
• Target enrollment: 0
• Participant gender: All

Summary

Tuberculosis (TB) treatment is long and complex with the risk of poor treatment adherence and treatment failure. Several attempts to shorten treatment of drug-susceptible TB have been unsuccessful. However, recent data support a shortened regimen for mild and moderate pulmonary TB and simultaneous optimization of rifampicin (RIF) and pyrazinamide (PZA).

This phase II clinical study aim to investigate a strategy to shorten TB treatment by exploring safety and drug exposure of a high-dose sterilizing TB regimen.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Linkoeping
• Collaborators: Kalmar County Hospital; Karolinska University Hospital; Linkoeping University; Ryhov County Hospital
• Treatments: Ethambutol; Isoniazid; Pyrazinamide; Rifampin

Criteria

Inclusion Criteria:

• Patient 18 years and older

• Confirmed pulmonary TB (positive Mtb culture or positive polymerase chain reaction (PCR) Mtb-complex)

• Intended to start on first-line TB treatment

• HIV negative

• BMI >17

• Written Informed Consent

• Women of childbearing potential should agree on adequate contraceptives during treatment period and have a negative pregnancy test prior to treatment initiation

Exclusion Criteria:

• Not able to provide informed consent/unable to assimilate study information

• Concomitant infectious disease that requires treatment

• Known allergy to rifamycins, isoniazid, pyrazinamide, ethambutol or history of severe sideeffect to any of the drugs

• Drug-induced inflammatory liver diseases in medical history

• History of acute liver disease

• On-going liver disease including hepatitis and elevated transaminase levels >x5 upper normal limit

• Porphyria

• Drug-drug interaction between concomitant drugs and rifampicin that could not be bridged by dose-adjustment of the concomitant drug

• Jaundice

• Acute gout

• Treatment of active TB during the last year

• Drug resistance to RIF, INH, PZA or EMB

• Miliary TB

• Pulmonary TB with smear positivity grade 3 and/or chest X-ray grading equal to advanced TB

• Extrapulmonary TB without pulmonary TB

• Pregnancy and breast-feeding

• Immunosuppressive condition

• Heart failure (NYHA class III and IV)

• Renal failure with estimated glomerular filtration rate (eGFR) <50 mL/min

• Dysregulated diabetes mellitus

• Alcohol and drug abuse

• Weight <35 kg or >90 kg

• Participation in other clinical trial (investigating a drug) within the last 30 days prior to study inclusion

• Person who the investigator, after consultation with the central contact persons of the study, finds by other reason than the above listed not suitable for study participation