VDOT for Monitoring Adherence to LTBI Treatment (VMALT): A Randomized Controlled Trial of Cell Phone Video Directly Observed Therapy to Monitor Short-Course LTBI Treatment (2015-2020)

 

Funded by NIAID grant U01-AI116392; PI: Richard S. Garfein, PhD, MPH

www.ClinicalTrials.gov. Study Identifier: NCT02641106

Over two billion persons worldwide are latently infected with the M. tuberculosis (Mtb) bacteria and are at risk for progressing to active TB disease. In the U.S., most active TB disease occurs in foreign-born persons, many of whom had latent tuberculosis infection (LTBI) that reactivated after immigrating. It is, therefore, critical that foreign-born and others with LTBI at increased risk for reactivation (e.g., persons coinfected with HIV, contacts of active TB cases) receive effective treatment if the U.S. is to achieve its TB elimination goals. Despite studies showing that treatment with the standard 9-month course of daily self-administered isoniazid (9H-SAT) reduces LTBI reactivation risk by 75%-90% and mortality risk among HIV co-infected persons by over 50%, less than half of eligible persons in the U.S. initiate treatment and only 50%-65% complete it primarily due to its long treatment duration. As such, only 300,000 of the approximately 10-15 million persons with LTBI in the U.S. are treated annually. A 3-month regimen of weekly isoniazid [H] and rifapentine [P] (3HP) was found to be as effective as the standard 9H-SAT regimen, completely changing the LTBI treatment landscape for the first time in decades. Due to its shorter regimen and fewer side-effects, 3HP promises to greatly improve LTBI treatment compliance and completion rates, ultimately decreasing TB reactivation rates in the U.S. However, uptake of the 3HP regimen is slow because the CDC advises only using the regimen with directly observed therapy (DOT), in which patients are watched taking each medication dose in-person. TB control programs lack resources to provide DOT for all patients with LTBI given that DOT is labor intensive, requires transportation, limits administration to business hours, restricts patient activities, and is impractical when patients travel frequently or live far from health clinics. Building on our novel mobile health (mHealth) approach called Video Directly Observed Therapy (VDOT), which has been used by health departments to monitor active TB patients via mobile phones, this study will assess whether VDOT can also be used to monitor short-course LTBI treatment with 3HP.

The goal of this randomized controlled trial is to determine whether adherence monitoring for short-course LTBI treatment using videos recorded and sent via mobile phones (VDOT) is superior to clinic-based in-person DOT in terms of treatment completion, timely medication dosing, patient acceptability, and cost-effectiveness.

Specific aims of this study are:

1. To determine whether LTBI treatment completion and adherence are greater for patients treated with 3HP administered via VDOT versus in-person DOT, and to identify patient factors associated with improved outcomes;

2. To compare acceptability of treatment by patients on VDOT versus in-person DOT, and identify factors associated with differences in acceptability;

3. To calculate the cost-effectiveness of VDOT compared to in-person DOT for administering 3HP.

To address the study aims, individuals in San Diego County who are prescribed 3HP for LTBI treatment by their physician are enrolled and randomly assigned to medication adherence monitoring via VDOT (intervention arm) or traditional, clinic-based in-person DOT (control arm) (n=155/arm).  Patients will be recruited through the San Diego County TB Control and Refugee Health Program (TCRHP) clinics, UCSD Student Health Services, and San Ysidro Health Center. Participants assigned to VDOT are loaned a smartphone with service and taught to record videos of themselves taking each weekly medication dose. Videos are automatically encrypted and uploaded to a secure server where clinic staff watch the videos to document medication ingestion. Patients in the in-person DOT arm visit the clinic each week to be observed taking their LTBI medication by a clinic staff member. Medication adherence will be monitored for all participants until they have taken all 12 doses or 16 weeks (limit recommended by the CDC to complete treatment). To compare treatment adherence rates and patient acceptance across trial arms, participants will complete brief (20 minute) baseline and follow-up assessment interviews to obtain information about potential confounders and effect modifiers of adherence and participant acceptance regarding their treatment administration method. Cost-benefit analyses will also be conducted to assist in developing policies around the use of VDOT for 3HP.

Principal Investigator: Richard S. Garfein, PhD, MPH

Co-Investigators: Constance Benson, Lin Liu

Study Coordinator: Jazmine Cuevas-Mota

Research Team: Valerie Mercer (Field Coordinator), Erin South, Fred Raab, Phil Rios

Collaborators: Jeannette Aldous, Antonette Antonio, Paulina Bobenrieth, Marti Brentnall, Ronelle Campbell, Joseph Capena, Donald Catanzaro, Yi-Ning Cheng, Janette L. Dubski, Lorena Gonzalez-Fabiny, Jackie Kersey-Hardrick, Lin Liu, Audrey Lopez, Stacie San Miguel, Maria Luisa Moore, Ryan Moran, Daniel Park, Regina Sandoval, Madeline Slater, Amish Talwar, Sayone Thihalolipavan, Sandi Thomas, and Wilma J. Wooten.