Clinical Trial: Study 33: Adherence to Latent Tuberculosis Infection Treatment 3HP SAT Versus 3HP DOT

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: TBTC Study 33. An Evaluation of Adherence to Latent Tuberculosis Infection (LTBI) Treatment With 12 Doses of Once Weekly Rifapentine (RPT) and Isoniazid (INH) Given as Sel

Brief Summary:

The study is an open label, multicenter, randomized (three arms: DOT (standard control), SAT, SAT with SMS reminders) controlled clinical trial. The trial is conducted in patients diagnosed with latent tuberculosis infection (LTBI) who are recommended for treatment. The primary objective is to evaluate adherence to a three-month (12-dose) regimen of weekly rifapentine and isoniazid (3RPT/INH) given by directly observed therapy (DOT) compared to self-administered therapy (SAT). The secondary objectives:

• To compare the treatment completion rates between participants randomized to SAT without reminders versus SAT with weekly SMS reminders
• To evaluate the timing of doses and patterns of adherence to once weekly RPT/INH among participants who complete treatment and those who discontinue therapy prior to completion.
• To determine the availability and acceptability of using SMS reminders among all patients consenting to participate in the study.
• To determine the toxicity and tolerability by comparing the rates of any drug-related grade 3 or 4 adverse events or death between the DOT arm and the SAT arms (both combined and individually)
• To compare the frequency, timing, and causes for failure to complete treatment between the DOT arm and the SAT arms
• To collect patient-specific cost data related to the 3 treatment arms
• To describe the pattern of antituberculosis drug resistance among Mycobacterium tuberculosis strains cultured from participants who develop active TB.

Detailed Summary:

The World Health Organization (WHO) estimates that approximately 2.3 billion people are infected with Mycobacterium tuberculosis. Approximately 1.7 million people die of TB each year, the second most common infectious cause of death in the world. In order to improve TB control worldwide, an affordable, effective, short course treatment for latent TB infection (LTBI) is a global priority.

Candidates for LTBI treatment are those persons with a positive TST or IGRA, particularly if they also have risk factors for progressing to active TB, including individuals likely to be recently infected. The Prevent TB Study (TBTC Study 26) was an open-label, randomized, phase III controlled clinical trial with over 8,000 high risk TST reactors enrolled. The study compared rifapentine and INH (3RPT/INH) given once-weekly by directly observed treatment (DOT) for 3 months (12 doses) compared with 9 months of daily, self-administered INH. The results demonstrated the safety and efficacy of the shorter regimen. Moreover, the once weekly therapy had significantly higher treatment completion rates than the standard 9 INH regimen.

One of the most effective strategies for assuring adherence with therapy is to have each dose of medication directly administered by a health care worker who observes and records the ingestion of the drugs. DOT for active TB has been successfully used in many settings to improve treatment completion, however cost and logistical constraints of DOT remain. The estimated cost of giving 12 weekly DOT doses to all LTBI patients is likely prohibitive for TB control programs worldwide. This may lead to a decreased uptake of the new regimen or implementation using SAT where adherence has not been studied. Therefore, to apply the Prevent TB study results more broadly, a new study evaluating treatment completion of 3 RPT/INH giv
Sponsor: Centers for Disease Control and Prevention

Current Primary Outcome: Treatment completion rate. [ Time Frame: Up to 16 weeks from start of treatment. ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Treatment completion rates between the DOT arm and the SAT arm with SMS reminders [ Time Frame: Up to 16 weeks from start of treatment. ]
• Treatment completion rates between the DOT arm and the SAT arm without SMS reminders. [ Time Frame: Up to 16 weeks from start of treatment. ]
• Treatment completion rates between the SAT arm with SMS reminders and the SAT arm without SMS reminders. [ Time Frame: Up to 16 weeks from start of treatment. ]
• Rates of treatment discontinuation by category. [ Time Frame: Up to 16 weeks from start of treatment. ]

  Categories of treatment discontinuation include:

  • due to adverse events
  • due to patient choice
  • due to inability to locate patient
  • other
• Rates of SMS reminders utilization. [ Time Frame: Up to 16 weeks from start of treatment. ]
• Rates of any drug-related grade 3, 4, or 5 adverse events between the DOT arm and the SAT arms (both combined and individually) [ Time Frame: Up to 20 weeks from start of treatment. ]
• Rates and timing of treatment discontinuations between the DOT arm and the SAT arms (both combined and individually). [ Time Frame: Up to 16 weeks from start of treatment. ]

  This includes discontinuations due to:

  • non-adherence
  • any adverse event (AE)
  • a diagnosis of active TB
  • other reasons
• Cost of treatment (in USD or QALY) associated with adverse events between the DOT arm and the SAT arms (both combined and individually). [ Time Frame: Up to 20 weeks from start of treatment. ]
• Rates of antituberculosis drug resistance among Mycobacterium tuberculosis strains cultured from patients who develop active TB between the DOT arm and the SAT arms (both combined and individually). [ Time Frame: up to 2 years from start of treatment. ]

Original Secondary Outcome: Same as current

Information By: Centers for Disease Control and Prevention

Dates:
Date Received: February 10, 2012
Date Started: September 2012
Date Completion:
Last Updated: July 30, 2015
Last Verified: July 2015