Precision Rifampin Trial for Personalized Dosing — P-RIF  

Tuberculosis Clinical Trial

Official title: Precision Rifampin (P-RIF) Trial for Personalized Dosing in Active Tuberculosis Disease

Status Not yet recruiting

Clinical Trial Summary

Individual pharmacokinetic variability is an important driver of tuberculosis (TB) treatment failure particularly among undernourished populations, and that suboptimal serum drug concentrations are associated with delayed response to treatment, death, and acquired bacterial drug resistance. Serum drug exposures can be approximated by urine excretion as measured by spectrophotometry, replacing the need for specialized equipment for serum testing. Anti-TB pharmacokinetic variability has also been associated with enteric pathogen burden. The overall hypothesis is that urine spectrophotometry will identify people with below-target rifampin serum concentrations, which can be corrected to target levels after dose adjustment as confirmed by serum mass spectrometry. Therefore, this protocol includes a clinical trial to assess efficacy and safety of rifampin dose adjustment based on urinary excretion levels among adults and children who are being treated for drug-sensitive pulmonary TB at our longstanding collaborative research site in Haydom Lutheran Hospital, Tanzania.

Clinical Trial Description

This is a single-site trial at Haydom Lutheran Hospital, a regional referral hospital level in Manyara Region of northern Tanzania. The primary objective: Among children and adults in Tanzania initiating treatment for drug-susceptible pulmonary TB, perform urine spectrophotometric testing for rifampin, and collect serum throughout the 24 hour dosing interval for later concentration measurement by gold-standard mass spectrometry and comparative pharmacokinetics. Patients with urine rifampin excretion below target will undergo incremental dose increase and urine spectrophotometry and serum collection will be repeated. Stool will also be evaluated at regular intervals to understand the association with enteropathogen burden and effects on rifampin absorption, urine excretion, and serum exposures. Participants will randomized to an early group where urine spectrophotometry and dose adjustment is performed at Day 14 after treatment initiation, or a delayed group where the intervention is performed at Day 21. Primary efficacy endpoint is the proportion of subjects in the early and delayed groups that reach serum target AUC0-24 (35 ug/mL for adults; 31.7 ug/mL for children) at Day 21, before the urine based dose adjustment is made in the delayed group. Primary safety endpoint is the number of severe adverse events. Secondary endpoints include: time to sputum culture conversion to negative, weight change. Time to culture conversion and weight change are stratified by age given pediatric populations are more likely to be culture negative and clinically diagnosed with weight gain a central measurement of treatment response. ;

Related Conditions & MeSH terms

• Tuberculosis

• NCT number: NCT06318416
• Study type: Interventional
• Source: University of Virginia
• Contact: Scott Heysell, MD, MPH
• Phone: 4342439064
• Email: skh8r@uvahealth.org
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: July 1, 2024
• Completion date: January 30, 2028