Precision Rifampin Trial for Personalized Dosing

Launched by UNIVERSITY OF VIRGINIA · Mar 12, 2024

Keywords

ClinConnect Summary

The Precision Rifampin Trial is studying how to personalize the dosage of a medication called rifampin for people being treated for tuberculosis (TB). This is important because some patients, especially those who are undernourished, may not get the right amount of the drug in their system, which can lead to treatment failure. The trial aims to use a simple urine test to measure how much rifampin is being excreted, which can help adjust the dosage to ensure it’s effective. This trial will take place at the Haydom Lutheran Hospital in Tanzania and will involve both adults and children diagnosed with active, drug-susceptible pulmonary TB.

To participate in this trial, individuals must be at least 3 years old and diagnosed with specific types of TB. Participants will begin a combination treatment that includes rifampin and will be monitored throughout the study. However, some people may not be eligible, such as those with certain health conditions like severe kidney disease or those who are pregnant. Participants can expect to undergo urine tests, and their dosing may be adjusted based on the results to optimize their treatment. The trial is not yet recruiting, but it represents an exciting approach to improving TB treatment outcomes.

Gender

ALL

Eligibility 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).