Options for Delivering Isoniazid-Rifapentine (3HP) for TB Prevention: the 3HP Options Implementation Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,656
- 试验地点
- 1
- 主要终点
- Proportion of Participants Who Accepted and Completed 3HP
研究概览
简要总结
The Options for Delivering Isoniazid-Rifapentine (3HP) for TB Prevention (3HP Options Implementation Trial) study will be a three-arm, open-label, parallel, randomized trial. This hybrid effectiveness-implementation trial will be conducted among people living with HIV infection (PLHIV) enrolled in HIV/AIDS care at the Mulago Immune Suppression Syndrome (i.e., HIV/AIDS) clinic in Kampala, Uganda. The overall objective of this study is to identify a patient-centered delivery strategy that will facilitate acceptance and completion of a three-month (12-dose) regimen of weekly rifapentine (RPT) and isoniazid (INH) by PLHIV enrolled in routine HIV/AIDS care in a high HIV/TB burden country. The primary outcome will be acceptance and completion of 3HP. Additional objectives will be to evaluate the implementation and cost-effectiveness of each delivery strategy.
详细描述
The overall objective of this study is to identify a patient-centered strategy that will facilitate 3HP uptake by PLHIV in the context of routine HIV/AIDS care in a high HIV/TB burden country. The investigators' central hypothesis is that offering PLHIV an informed choice between directly observed therapy (DOT) and self-administered therapy (SAT) delivery strategies that are optimized to overcome key barriers to treatment adherence will result in greater acceptance and completion of 3HP. To test this hypothesis, the investigators will conduct a pragmatic randomized trial of three optimized strategies for delivering 3HP. Eligible participants will be randomized to one of three arms to receive latent tuberculosis infection (LTBI) treatment with once weekly INH and RPT for 12 weeks given by either facilitated DOT, facilitated SAT, or an informed choice between facilitated DOT and facilitated SAT (with the assistance of a decision aid tool).
Primary Objective: To compare the uptake of 3HP under three delivery strategies: 1) Facilitated DOT; 2) Facilitated SAT; and 3) Informed patient choice (using a decision aid) between facilitated DOT and facilitated SAT. The primary outcome will be defined as the proportion of eligible participants who accept treatment and take at least 11 of 12 doses of RPT/INH within 16 weeks of treatment initiation. Study staff will assess medication dosing using clinic records for participants taking 3HP by DOT and using a combination of 99DOTS (Everwell Health Solutions, India) digital medication adherence technology records and pill counts at refill visits for participants taking 3HP by SAT.
Secondary Objectives:
- To estimate the costs and compare the cost-effectiveness of the three strategies for delivering 3HP.
- To identify processes and contextual factors that influence patient acceptance and completion of 3HP under each delivery strategy.
- To identify clinic-level barriers to adoption and implementation of 3HP under each delivery strategy.
- To determine the proportion of patients for whom 3HP treatment is discontinued due to adverse events/intolerance.
- To determine the cumulative 16-month incidence of active TB in each arm, categorized as definite (positive sputum Xpert MTB/RIF or culture) or probable (TB medications started at the discretion of a clinician, with evidence of subsequent improvement).
- To determine the cumulative 28-month incidence of active TB in each arm, categorized as definite (positive sputum Xpert MTB/RIF or culture) or probable (TB medications started at the discretion of a clinician, with evidence of subsequent improvement).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •HIV-positive client engaged in care at the Mulago ISS clinic
- •Weight ≥40kg
- •Age 18 years or older
- •Capacity to provide informed consent in English or Luganda
排除标准
- •Suspicion of active TB based on positive World Health Organization (WHO) symptom screen AND elevated point-of-care (POC) C-reactive protein (CRP), or current or planned TB treatment
- •Actively taking an antiretroviral medication contraindicated for use with rifapentine under contemporary WHO or Ugandan policy
- •Contact of a TB patient with known resistance to isoniazid or rifamycins
- •Women who are pregnant, breast feeding or intending to get pregnant in the next 120 days
- •Prisoners
- •Previously completed treatment for active TB or at least 6 months of isoniazid preventive therapy within past 2 years
- •Not intending to remain within 25 km of the Mulago ISS clinic during the study period or to receive further care at the Mulago ISS clinic
- •Lack of access to a mobile telephone or lack of willingness to receive SMS reminders
- •Pre-existing documentation of clinical liver disease.
- •History of sensitivity or intolerance to isoniazid or rifamycins
- •Another household member already enrolled in the study (household members cannot be effectively randomized to different arms)
- •Actively taking medication contraindicated for use with rifamycin (e.g., warfarin, phenytoin)
- •Mixed methods and health economic sub-studies will include a subset of participants enrolled in the trial, as well as clinic administrators and clinicians (clinical officer, doctor, nurse or pharmacist) involved in 3HP delivery at the Mulago ISS clinic.
结局指标
主要结局
Proportion of Participants Who Accepted and Completed 3HP
时间窗: Within 16 weeks of treatment initiation
The count of eligible participants who accept treatment and take at least 11 of 12 once weekly doses of rifapentine (RPT)/isoniazid (INH) within 16 weeks of treatment initiation divided by the count of those randomized.
次要结局
- Cost Effectiveness (Patient Perspective)(At the conclusion of the study period, estimated 3 years)
- Cost Effectiveness (Overall Perspective)(At the conclusion of the study period, estimated 3 years)
- Proportion of Participants Who Completed 3HP Treatment(Within 16 weeks of treatment initiation)
- Cumulative Incidence of Tuberculosis (TB)(from date of 3HP treatment completion (11/12 doses) or once reached 16 weeks (regardless of number of doses taken) until time of active TB diagnosis or treatment initiation, death, loss to follow-up or end of the 12-month post-treatment follow-up period)
- Cumulative Incidence of TB(from date of 3HP treatment completion (11/12 doses) or once reached 16 weeks (regardless of number of doses taken) until time of active TB diagnosis or treatment initiation, death, loss to follow-up or end of the 24-month post-treatment follow-up period)
- Visit Cost Reimbursement(On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks)
- Time to Complete Clinic Visit - Median Minutes(On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks)
- Dosing Confirmation Via 99DOTS (SAT Only)(On the same day as each scheduled dose throughout study completion, an average of 16 weeks)
- Follow up (Phone Calls or Home Visits) for Negative Response to Weekly SMS or IVR Phone Call check-in (SAT Only)(24 hours after negative response throughout study completion, an average of 16 weeks)
- Costs of Preventive Services(Through study completion, an average of 16 weeks)
- Barriers to 3HP Delivery From the Provider/Clinic Perspective(At the conclusion of the study period, estimated 3 years)
- Proportion of People Who Discontinued 3HP Treatment Due to Adverse Events/Intolerance(Within 16 weeks of treatment initiation)
- Time to Complete Clinic Visit - Mean Minutes(On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks)
- Barriers to 3HP Completion From the Patient Perspective(Through study completion, an average of 16 weeks)
- Proportion of Participants Who Accepted 3HP Treatment(Within 16 weeks of treatment initiation)
- Cost Effectiveness (Health System Perspective)(At the conclusion of the study period, estimated 3 years)
- Visit Cost Reimbursement - Overall(Through study completion, an average of 16 weeks)
- Short Messages Service (SMS) or Interactive Voice Response (IVR) Phone Call Reminders Delivered - Clinic Visits(The day before each 3HP clinic visit throughout study completion, an average of 16 weeks)
- Screening for Active TB(On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks)
- Screening for Side Effects(On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks)
- SMS or IVR Phone Call Reminders Delivered - Medication Dosing (SAT Only)(The day before each scheduled dose throughout study completion, an average of 16 weeks)
- SMS or IVR Phone Calls Delivered - Weekly check-in (SAT Only)(On the same day as each scheduled dose throughout study completion, an average of 16 weeks)
- SMS or IVR Phone Call Reminders Delivered - Missed Dose (SAT Only)(24 hours after missed scheduled dose throughout study completion, an average of 16 weeks)
- SMS or IVR Phone Call Missed Appointment Reminders Delivered(24 hours after missed scheduled appointment throughout study completion, an average of 16 weeks)
- Participant Satisfaction(Through study completion, an average of 16 weeks)