Personalized rifampin dosing guided by a urine test
Precision Rifampin (P-RIF) Trial for Personalized Dosing in Active Tuberculosis Disease
This trial will test whether a simple urine spectrophotometry test can identify adults and children with low rifampin levels so clinicians can increase doses to reach target blood exposure during treatment for drug‑sensitive pulmonary TB.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 200 (estimated) |
| Ages | 3 Years and up |
| Sex | All |
| Sponsor | University of Virginia Academic / other |
| Locations | 1 site (Haydom) |
| Trial ID | NCT06318416 on ClinicalTrials.gov |
What this trial studies
This single-site, randomized Phase 1 trial at Haydom Lutheran Hospital in northern Tanzania uses urine spectrophotometry to approximate rifampin exposure and compares early versus delayed urine-guided dose adjustment. Participants provide timed urine and serum samples across the 24-hour dosing interval with serum later measured by gold-standard mass spectrometry to confirm exposures. Those with below-target urine rifampin excretion receive incremental dose increases and repeat sampling, and stool samples are collected to study enteropathogen burden and its effect on absorption. The primary efficacy endpoint is the proportion reaching predefined serum AUC0-24 targets by Day 21, and the primary safety endpoint is the number of severe adverse events.
Who should consider this trial
Good fit: Ideal candidates are people age 3 and older with newly diagnosed rifampin-susceptible pulmonary TB who are starting standard first-line therapy and live within the predefined clinic follow-up area.
Not a fit: Patients with rifampin-resistant TB, significant kidney disease, urinary incontinence or oliguria that prevents reliable urine collection, or those unable to remain in the study area are unlikely to benefit from this approach.
Why it matters
Potential benefit: If successful, a low-cost urine test could let clinicians identify and correct low rifampin exposure, improving treatment success and reducing the risk of resistance in resource-limited settings.
How similar studies have performed: Prior pharmacokinetic work has shown that urine rifampin measures correlate with serum exposure and that PK variability affects outcomes, but using urine spectrophotometry to guide dose increases in a randomized clinical context is relatively novel and not yet proven.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. Age 3 or older 2. Diagnosed with active, rifampin-susceptible, pulmonary TB- sputum positive for M. tuberculosis complex without rpoB mutation, or culture for M. tuberculosis with conventional rifampin susceptibility OR among children unable to expectorate, meeting confirmed or probable consensus clinical case definitions for intrathoracic childhood TB 3. Initiating combination anti-TB therapy with isoniazid, rifampin, pyrazinamide, and ethambutol 4. Subject or guardian is able to provide informed consent; and for children 7 years or older, provide assent 5. Stated willingness to comply with all trial procedures and availability for the duration of the trial 6. Resident within a pre-defined geographic area to ensure TB clinic follow-up Exclusion Criteria: 1. Urinary incontinence: may complicate urine collection 2. Oliguria: may complicate urine collection and limit correlation of urinary excretion and serum concentrations 3. Kidney disease, defined as a glomerular filtration rate (GFR) \< 60 mL/min: In 5R01 AI137080, those adults with GFR \< 60 mL/min had reduced correlation or urinary rifampin excretion and serum concentrations. 4. Severe anemia, defined as a hemoglobin level less than 7 g/dL: given planned phlebotomy 5. Elevated liver function tests, defined as DAIDS grade 3 or above (ALT or AST \>/= 5 x upper limit of normal): may confound potential toxicity signals of dose adjustment strategy 6. Pregnancy: Urine rifampin spectrophotometry has not been studied in pregnant people, higher dose rifampin also less studied in pregnancy, and may confound potential toxicity signals (e.g. elevated liver function tests in pregnancy). Urine pregnancy test will be completed at screening in people of child-bearing potential. Child-bearing potential is defined as a person able to menstruate (menstruation in the last 12 months) and not receiving a form of contraception with less than \<1% failure rate (oral levonorgestrel, IUD or etonogestrel implant). 7. Weight \<10.0 kg (dose increase may exceed 30mg/kg/dose) 8. Current treatment with a drug known to have significant interaction with anti-TB therapy 9. Excessive alcohol use? (for example, Men consuming \> 14 standardized drinks per week and/or \> 4 drinks per day OR women consuming \>7 standardized drinks per week, and/or \>3 drinks per day, or at the discretion of the investigator(s).
Where this trial is running
Haydom
- Haydom Lutheran Hospital — Haydom, Tanzania (Recruiting)
Study contacts
- Study coordinator: Scott Heysell, MD, MPH
- Email: skh8r@uvahealth.org
- Phone: 4342439064
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.