Clinical trial NCT03266003: An Evaluation of Traditional Directly Observed Therapy (DOT) and Electronic DOT for TB Treatment
Official title: An Evaluation of Traditional Directly Observed Therapy and Electronic Forms of Directly Observed Therapy for Tuberculosis Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tuberculosis
Drug-resistant Tuberculosis
Adherence, Medication
Adherence, Patient
Keywords: Tuberculosis
Directly observed therapy
Adherence
Video assisted directly observed therapy
Electronic directly observed therapy
Mobile health
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
Collaborators: name: New York City Department of Health and Mental Hygiene
name: Columbia University
First posted: 2017-08-29
Enrollment: 216
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

DOT entails a trained "observer" acceptable to both the patient and the health system being present to monitor treatment adherence as patients swallow anti-TB drugs. In the United States, DOT remains a cornerstone of TB control. While DOT represents the treatment standard, the implementation of DOT has been modified by some programs in an effort to reduce costs and conserve program resources. In the U.S., efforts recently have sought to utilize advances in communication technology to facilitate the implementation of DOT.

This study will evaluate traditional approaches to DOT compared to DOT by electronic methods. The study will be based within, and primarily conducted by the New York City Department of Health and Mental Hygiene (NYC DOHMH), Bureau of Tuberculosis Control (BTBC) clinics. This will enable the study to be to be conducted in a programmatic setting and reflect "real-life" situations.

Hypothesis: Directly observed therapy (DOT) that employs electronic communication methods (eDOT) is a non-inferior approach to monitor treatment adherence, compared to traditional forms of DOT, in which a trained person is in the physical presence of patients as anti-TB drugs are ingested (ipDOT).

Design: This will be a U.S.-based, 1 site (with 4 clinic settings), randomized, cross-over, 2-arm, non-inferiority trial with randomization to either traditional in-person DOT (ipDOT) or electronic DOT (eDOT)\*, at the time outpatient treatment begins within participating health department clinics.

\*Secondary analyses will evaluate DOT conducted in "real time" or "live" (eDOT-live) compared to DOT that uses a recorded video (eDOT-recorded).

Population:Patients newly diagnosed with drug-sensitive or non-rifamycin resistant TB.

Site: Four clinics of the New York City Department of Health and Mental Hygiene, Bureau of Tuberculosis Control.

Study Duration: Duration per participant is approximately 6 months.

Description of Intervention: After providing written informed consent, participants will be randomly assigned to one of the following DOT study group assignments: (1) traditional in-person DOT (ipDOT) or (2) electronic DOT (eDOT).

Note: Patients and their providers will discuss and choose the type of eDOT they will use. The two options are: (2a) eDOT conducted "live" in which TB program staff interact with patients in real-time via a computer or phone application as they ingest their medication (eDOT-live), and (2b) eDOT in which patients record themselves ingesting their TB medication using "time-stamped, recorded" videos for TB program staff to review within 1 business day (24 hours), and verify that patients ingested their medication doses as scheduled (eDOT-recorded).

Following 20 observable medication doses under an initial DOT study group assignment participants will be assigned (crossed-over) to the opposite DOT method to collect data on another 20 observable medication doses. Specifically, participants who initially received ipDOT will switch to eDOT. Participants initially assigned to eDOT will switch to ipDOT.

At the conclusion of this Cross-Over Period with 40 observable medication doses, participants will continue treatment using their preferred DOT method.

Eligibility criteria: Inclusion Criteria:

Individuals must meet the following inclusion criteria in order to participate in this study:

1. 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.
2. Physician determines the patient may be treated with any treatment regimen for non-rifamycin resistant TB approved by the NYC DOHMH TB program.
3. Individuals found to have Isoniazid (INH) resistant disease are eligible for inclusion.
4. Age \>18 years or older
5. Age 12 to 17 years, with the consent of a parent or legal guardian
6. 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.
7. No plans to move out of the catchment areas of the participating TB program sites within 9 months of enrollment.
8. Willingness to comply with study procedures and provide written informed consent prior to study enrollment.
9. 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:

1. 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.
2. Prescribed any injectable, anti-TB medication as part of an outpatient treatment regimen.
3. 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.
4. 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.
5. Less than 12 years of age.
6. Patients 12-17 years of age, whose parents or legal guardians refuse to provide consent.
7. Incarceration, institutionalization, or other involuntary detention.
8. Plans to move out of the catchment areas of the participating TB program sites in less than 9 months from the day of enrollment.
9. Previously enrolled in this study.
10. Currently enrolled in a clinical trial that prohibits enrollment in another study.
11. Other medical conditions that, in the investigator's or the clinic physician's judgment, make study participation not in the individual's best interest.

Primary outcomes:
measure: Proportion of medication doses directly observed
timeFrame: 6 months
Secondary outcomes:
measure: Proportion of medication doses not directly observed
timeFrame: 6 months
measure: Medication side effects
timeFrame: Up to 13 weeks
Other outcomes:
measure: Patients' demographic, social, and medical characteristics associated with treatment adherence
timeFrame: 6 months
measure: Treatment outcomes
timeFrame: 6 months
measure: Participants' preferred DOT method at the conclusion of the cross-over period.
timeFrame: 8 -13 weeks
measure: Patient Opinion Questionnaire
timeFrame: 8-13 weeks
Locations:
city: Bronx
country: United States
facility: Morrisania Chest Center
state: New York
city: Brooklyn
country: United States
facility: Fort Greene Chest Center
state: New York
city: Jackson Heights
country: United States
facility: Corona Chest Center
state: New York
city: New York
country: United States
facility: Washington Heights Chest Center
state: New York
Study officials:
affiliation: New York City DOHMH, Bureau of Tuberculosis Control
name: Joseph Burzynski, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Burzynski J, Mangan JM, Lam CK, Macaraig M, Salerno MM, deCastro BR, Goswami ND, Lin CY, Schluger NW, Vernon A; eDOT Study Team. In-Person vs Electronic Directly Observed Therapy for Tuberculosis Treatment Adherence: A Randomized Noninferiority Trial. JAMA Netw Open. 2022 Jan 4;5(1):e2144210. doi: 10.1001/jamanetworkopen.2021.44210.