An Evaluation of Traditional Directly Observed Therapy and Electronic Forms of Directly Observed Therapy for Tuberculosis Treatment
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 216
- Locations
- 4
- Primary Endpoint
- "Percentage of Medication Doses Directly Observed (Modified ITT Analysis)"
Study Overview
Brief Summary
This study is a U.S.-based, 1 site (with 4 clinical settings), randomized controlled trial (with funding from the Centers for Disease Control and Prevention's (CDC) Antibiotic Resistance Solutions Initiative) that will be implemented to evaluate traditional directly observed therapy (DOT) and electronic forms of DOT (eDOT) for tuberculosis (TB) treatment. The trial will assess whether eDOT that employs electronic communication methods, such as video via computer or cellphone, is a non-inferior approach to monitor TB treatment adherence, compared to traditional in-person DOT (ipDOT), in which a trained person is in the physical presence of patients as anti-TB drugs are ingested. ipDOT is the single best intervention proven to be successful when it comes to TB patients' adherence to therapy (which reduces risk of acquired drug resistance). However, ipDOT is resource intensive and many times challenging to facilitate in-person. If eDOT is found to be non-inferior to ipDOT, health departments and other clinicians might be able to provide eDOT to certain populations of TB patients in a more flexible and potentially cost-saving manner.
Detailed Description
Tuberculosis (TB) is among the most common infectious diseases and cause of death worldwide. The bacteria that causes TB, Mycobacterium tuberculosis (Mtb), is spread when a person with TB disease of the lungs or throat coughs, speaks, or sings. These bacteria can float in the air for several hours, depending on the environment. Persons who breathe in the air containing these TB bacteria can become infected.
The World Health Organization (WHO) estimates that 9.6 million became ill with TB in 2014. Among this group, approximately 480,000 persons became ill with multidrug-resistant TB (MDR TB), which is TB caused by bacteria that are resistant to at least isoniazid and rifampin, the two most potent TB drugs used to treat persons with TB disease. Extensively drug resistant (XDR) strains of TB were reported by 105 countries in 2015. As such, the National Strategy for Combatting Antibiotic Resistant Bacteria (CARB) has designated Mtb a SERIOUS threat level pathogen.
Completion of treatment by persons with TB disease represents the optimal path to the prevention of morbidity and mortality, cure of the patient, interruption of transmission, and prevention of acquired drug resistance. The single best intervention in this regard has proven to be directly observed therapy (DOT).
DOT provides frequent interactions between the patient and the patient's healthcare team. This enables better monitoring and efficient response to medication side effects. This is especially important as medication side effects are among the top reasons patients are lost to follow-up during treatment therapy.
Experience in the U.S. in the 1990s demonstrated the efficacy of this intervention in the prevention and control of drug-resistant tuberculosis.Studies in the past 15 years in international settings have challenged the utility of DOT, but have been criticized for imperfect to poor design or implementation.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Health Services Research
- Masking
- None
Eligibility Criteria
- Ages
- 12 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Individuals must meet the following inclusion criteria in order to participate in this study:
- •All TB patients (both those with a confirmed diagnosis and those with a clinical diagnosis), started on treatment for non-rifamycin resistant TB, and eligible to receive DOT.
- •Physician determines the patient may be treated with any treatment regimen for non-rifamycin resistant TB approved by the NYC DOHMH TB program.
- •Individuals found to have Isoniazid (INH) resistant disease are eligible for inclusion.
- •Age >18 years or older
- •Age 12 to 17 years, with the consent of a parent or legal guardian
- •An address or residence location that is readily accessible for visiting, and willingness to inform the study team of any change of address during the treatment and follow-up period.
- •No plans to move out of the catchment areas of the participating TB program sites within 9 months of enrollment.
- •Willingness to comply with study procedures and provide written informed consent prior to study enrollment.
- •Individuals for whom a diagnosis of TB has been made clinically are eligible for study inclusion. Data may be collected from these patients related to all objectives with the exception of culture conversion.
Exclusion Criteria
- •An individual meeting any of the following exclusion criteria at the time of enrollment will be excluded from study participation:
- •At the time of enrollment, the patient's Mtb isolate is already known to be resistant to rifamycin or prescribed a non-rifamycin treatment regimen.
- •Prescribed any injectable, anti-TB medication as part of an outpatient treatment regimen.
- •Adverse reaction to initial doses of anti-TB medication (per NYC protocol) of sufficient severity that in the judgement of the clinician makes study participation not in the individual's best interest.
- •A cognitive or physical disability that prevents full participation in eDOT (e.g., vision, hearing, physically challenged, inability to swallow medications). Note: Exceptions will be made for those patients who crush pills in order to swallow the medication, or have a member of their household or a caregiver who can assist them for the duration of the study.
- •Less than 12 years of age.
- •Patients 12-17 years of age, whose parents or legal guardians refuse to provide consent.
- •Incarceration, institutionalization, or other involuntary detention.
- •Plans to move out of the catchment areas of the participating TB program sites in less than 9 months from the day of enrollment.
- •Previously enrolled in this study.
- •Currently enrolled in a clinical trial that prohibits enrollment in another study.
- •Other medical conditions that, in the investigator's or the clinic physician's judgment, make study participation not in the individual's best interest.
Arms & Interventions
Group 1: ipDOT followed by eDOT
Following 20 observable medication doses under an initial DOT study group assignment of in-person DOT (ipDOT), patients will be assigned (crossed-over) to electronic DOT (eDOT) to collect data on another 20 observable medication doses.
Intervention: Electronic DOT (Other)
Group 1: ipDOT followed by eDOT
Following 20 observable medication doses under an initial DOT study group assignment of in-person DOT (ipDOT), patients will be assigned (crossed-over) to electronic DOT (eDOT) to collect data on another 20 observable medication doses.
Intervention: In-person DOT (Other)
Group 2: eDOT followed by ipDOT
Following 20 observable medication doses under an initial DOT study group assignment of electronic DOT (eDOT), patients will be assigned (crossed-over) to in-person DOT (ipDOT) to collect data on another 20 observable medication doses.
Intervention: Electronic DOT (Other)
Group 2: eDOT followed by ipDOT
Following 20 observable medication doses under an initial DOT study group assignment of electronic DOT (eDOT), patients will be assigned (crossed-over) to in-person DOT (ipDOT) to collect data on another 20 observable medication doses.
Intervention: In-person DOT (Other)
Outcomes
Primary Outcomes
"Percentage of Medication Doses Directly Observed (Modified ITT Analysis)"
Time Frame: Time frame varied based on the participant's prescribed treatment regimen and phase of treatment; 20 doses of medication would require 8 to 13 weeks.
The proportion of observable medication doses directly observed by staff during in-person DOT and electronic DOT, analyzed using the modified intention-to-treat (Modified ITT) population. The unit of analysis is medication doses.
Percentage of Medication Doses Directly Observed (Empirical Analysis)
Time Frame: Cross-over period; 20 observable medication doses per DOT method (approximately 8 to 13 weeks depending on treatment regimen).
The proportion of observable medication doses directly observed by staff during in-person DOT and electronic DOT, analyzed using the empirical analysis population. The unit of analysis is medication doses.
Secondary Outcomes
- Reporting of Medication Side Effects(Time frame varied based on the participant's prescribed treatment regimen and phase of treatment; 20 doses of medication would require 8 -13 weeks.)
- Number of Medication Doses Not Directly Observed(During the cross-over period and continuation period, from treatment initiation until completion of tuberculosis treatment (approximately up to 6 months, depending on the prescribed treatment regimen).)