TuberculosisPhase 1P-RIFNCT06318416
Precision Rifampin Trial for Personalized Dosing
A Phase 1 study testing urine spectrophotometry for rifampin absorbance in people with Tuberculosis, run by University of Virginia at 1 site in Tanzania.
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. Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Tuberculosis
- What is being tested?
- urine spectrophotometry for rifampin absorbance
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteTanzania
- Study dates
- 1 Oct 2025to 1 Jun 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 3 or older
- 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
- Initiating combination anti-TB therapy with isoniazid, rifampin, pyrazinamide, and ethambutol
- Subject or guardian is able to provide informed consent; and for children 7 years or older, provide assent
- Stated willingness to comply with all trial procedures and availability for the duration of the trial
- Resident within a pre-defined geographic area to ensure TB clinic follow-up
Who cannot join
- Urinary incontinence: may complicate urine collection
- Oliguria: may complicate urine collection and limit correlation of urinary excretion and serum concentrations
- 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.
- Severe anemia, defined as a hemoglobin level less than 7 g/dL: given planned phlebotomy
- 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
- 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).
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- Weight <10.0 kg (dose increase may exceed 30mg/kg/dose)
- Current treatment with a drug known to have significant interaction with anti-TB therapy
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Tanzania1 site, 1 recruiting
- Recruiting
Haydom Lutheran Hospital
Haydom
Estomih Mduma, PhD, +255 789 558 662, estomduma@gmail.com
About this study
Official title: Precision Rifampin (P-RIF) Trial for Personalized Dosing in Active Tuberculosis Disease
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.
Read the detailed 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. Safety of dose adjustment strategy parameters include clinical adverse events, liver function tests, kidney function tests and hematological parameters
- Conditions
- Tuberculosis
- Being tested
- urine spectrophotometry for rifampin absorbance
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
urine spectrophotometry for rifampin absorbanceDiagnostic test
All participants will received conventional weight-based TB therapy, standard of care for active TB disease. After enrollment, participants will be randomized to early Day 14 or delayed Day 21 dose modification of rifampin informed by urine spectrophotometry where absorbance is determined above or below a threshold. Below a threshold, single tablets of rifampin are added to conventional fixed drug combination standard of care, above a threshold, no additional rifampin is added. Dose adjustment of rifampin may be up to ~30mg/kg and will be continued through day-56.
| Study group | Role | What they receive |
|---|---|---|
| Early | Experimental | Urine spectrophotometry for rifampin absorbance and rifampin dose adjustment at Day 14 Receives: Diagnostic Test: urine spectrophotometry for rifampin absorbance |
| Delayed | Experimental | Urine spectrophotometry for rifampin absorbance and rifampin dose adjustment at Day 21 Receives: Diagnostic Test: urine spectrophotometry for rifampin absorbance |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rifampin serum area under the concentration time curve for the 24 hour dosing interval
Primary efficacy endpoint is the proportion of subjects in the early and delayed group that reach serum target AUC0-24 (35 ug/mL for adults; 31.7 ug/mL for children).
Measured: 21 days
Adverse events
Primary safety endpoint is the number of serious adverse events
Measured: 56 days
Secondary outcomes (4)
Time to sputum culture conversion to negative
Time to sputum culture conversion to negative from pretreatment, Day 0, and serial sample collection as measured by mycobacterial load assay
Measured: 56 days
Weight change
Percent of weight change of total body weight in kilograms
Measured: 56 days
Enteropathogen burden
Total number of enteropathogen species as detected by stool multiplex PCR TaqMan Array Card
Measured: 14, 21 and 28 days after enrollment
Biomarkers of intestinal inflammation, permeability and intestinal mass
Serum citruline, stool myeloperoxidase, stool alpha-1-antitrypsin, stool neopterin
Measured: 14, 21, 28 days after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2024
- Study start1 Oct 2025
- Primary completion30 Dec 2027 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- Rutgers University, Haydom Lutheran Hospital
- Responsible party
- Principal investigator, Scott Heysell, MD, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06318416
- Sponsor's protocol ID
- HSR230382
- Acronym
- P-RIF
- Status last verified
- Jan 2026
- First submitted
- 12 Mar 2024
- Last updated
- 27 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Xie YL, Modi N, Handler D, Yu S, Rao P, Kagan L, Petros de Guex K, Reiss R, Siemiatkowska A, Narang A, Narayanan N, Hearn J, Khalil A, Woods P, Young L, Lardizabal A, Subbian S, Peloquin CA, Vinnard C, Thomas TA, Heysell SK. Simplified urine-based method to detect rifampin underexposure in adults with tuberculosis: a prospective diagnostic accuracy study. Antimicrob Agents Chemother. 2023 Nov 15;67(11):e0093223. doi: 10.1128/aac.00932-23. Epub 2023 Oct 25.
PubMed 37877727Thomas TA, Lukumay S, Yu S, Rao P, Siemiatkowska A, Kagan L, Augustino D, Mejan P, Mosha R, Handler D, Petros de Guex K, Mmbaga B, Pfaeffle H, Reiss R, Peloquin CA, Vinnard C, Mduma E, Xie YL, Heysell SK. Rifampin urinary excretion to predict serum targets in children with tuberculosis: a prospective diagnostic accuracy study. Arch Dis Child. 2023 Aug;108(8):616-621. doi: 10.1136/archdischild-2022-325250. Epub 2023 Apr 25.
PubMed 37171408
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Precision Rifampin (P-RIF) Trial for Personalized Dosing in Active Tuberculosis Disease
- ClinicalTrials.gov ID
- NCT06318416
- Acronym / sponsor ID
- P-RIF / HSR230382
- Conditions
- Tuberculosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- Rutgers University, Haydom Lutheran Hospital
- Study start
- 1 Oct 2025 (actual)
- Primary completion
- 30 Dec 2027 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 19 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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. Safety of dose adjustment strategy parameters include clinical adverse events, liver function tests, kidney function tests and hematological parameters
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early | Experimental | Diagnostic Test: urine spectrophotometry for rifampin absorbanceUrine spectrophotometry for rifampin absorbance and rifampin dose adjustment at Day 14 |
| Delayed | Experimental | Diagnostic Test: urine spectrophotometry for rifampin absorbanceUrine spectrophotometry for rifampin absorbance and rifampin dose adjustment at Day 21 |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Age 3 or older
- 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
- Initiating combination anti-TB therapy with isoniazid, rifampin, pyrazinamide, and ethambutol
- Subject or guardian is able to provide informed consent; and for children 7 years or older, provide assent
- Stated willingness to comply with all trial procedures and availability for the duration of the trial
Key exclusion criteria (9 listed)
- Urinary incontinence: may complicate urine collection
- Oliguria: may complicate urine collection and limit correlation of urinary excretion and serum concentrations
- 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.
- Severe anemia, defined as a hemoglobin level less than 7 g/dL: given planned phlebotomy
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| urine spectrophotometry for rifampin absorbanceAll participants will received conventional weight-based TB therapy, standard of care for active TB disease. After enrollment, participants will be randomized to early Day 14 or delayed Day 21 dose modification of rifampin informed by urine spectrophotometry where absorbance is determined above or below a threshold. Below a threshold, single tablets of rifampin are added to conventional fixed drug combination standard of care, above a threshold, no additional rifampin is added. Dose adjustment of rifampin may be up to ~30mg/kg and will be continued through day-56. | Diagnostic test | Delayed, Early |
Primary outcome
Rifampin serum area under the concentration time curve for the 24 hour dosing interval
Time frame: 21 days
Primary efficacy endpoint is the proportion of subjects in the early and delayed group that reach serum target AUC0-24 (35 ug/mL for adults; 31.7 ug/mL for children).
Adverse events
Time frame: 56 days
Primary safety endpoint is the number of serious adverse events
4 secondary outcomes
Time to sputum culture conversion to negative
Time frame: 56 days
Weight change
Time frame: 56 days
Enteropathogen burden
Time frame: 14, 21 and 28 days after enrollment
Biomarkers of intestinal inflammation, permeability and intestinal mass
Time frame: 14, 21, 28 days after enrollment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2026.
- Background: PubMed 37877727Xie YL, Modi N, Handler D, Yu S, Rao P, Kagan L, Petros de Guex K, Reiss R, Siemiatkowska A, Narang A, Narayanan N, Hearn J, Khalil A, Woods P, Young L, Lardizabal A, Subbian S, Peloquin CA, Vinnard C, Thomas TA, Heysell SK. Simplified urine-based method to detect rifampin underexposure in adults with tuberculosis: a prospective diagnostic accuracy study. Antimicrob Agents Chemother. 2023 Nov 15;67(11):e0093223. doi: 10.1128/aac.00932-23. Epub 2023 Oct 25.
- Background: PubMed 37171408Thomas TA, Lukumay S, Yu S, Rao P, Siemiatkowska A, Kagan L, Augustino D, Mejan P, Mosha R, Handler D, Petros de Guex K, Mmbaga B, Pfaeffle H, Reiss R, Peloquin CA, Vinnard C, Mduma E, Xie YL, Heysell SK. Rifampin urinary excretion to predict serum targets in children with tuberculosis: a prospective diagnostic accuracy study. Arch Dis Child. 2023 Aug;108(8):616-621. doi: 10.1136/archdischild-2022-325250. Epub 2023 Apr 25.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing urine spectrophotometry for rifampin absorbance in people with Tuberculosis, run by University of Virginia at 1 site in Tanzania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Scott Heysell, MD, MPH (4342439064, skh8r@uvahealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rifampin serum area under the concentration time curve for the 24 hour dosing interval (time frame: 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06318416, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2026.