Mobile-Directly Observed Therapy on Adherence to Hydroxyurea

Study Overview
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Brief Summary
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To examine the effect of mobile-directly observed therapy (mDOT) on adherence to HU (mDOT-HuA) adults with SCA at Muhimbili National Hospital (MNH) in Tanzania.

Detailed Description
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Background: Hydroxyurea (HU) has been demonstrated to be efficacious in reducing complications in individuals with Sickle Cell Anemia (SCA) but poor adherence is a barrier to improving outcomes in patients with SCA. Directly Observed Therapy (DOT) has been shown to improve adherence in various chronic diseases but there is limited data in adults with sickle cell anaemia (SCA). Methods and design: To examine the effect of mobile-directly observed therapy (mDOT) on adherence to HU (mDOT-HuA) adults with SCA at Muhimbili National Hospital (MNH) in Tanzania.The mDOT-HuA study is single centre, prospective, randomized, open label clinical trial. 100 participants with SCA with hemoglobin SS genotype, aged ≥18 years, living in urban Dar es Salaam and able and willing to participate in the study. Participants will be divided into two treatment arms; 50 in standard monitoring (SM) arm: will receive fixed dose HU therapy with standard monitoring. 50 in treatment mDOT arm: will receive fixed dose HU therapy with standard monitoring and a mobile direct observed web based medication adherence monitoring system. The primary outcome is adherence to HU as defined as medication possession ratio of ≥80 at end of 3 months of HU treatment and mDOT monitoring. Secondary outcomes will be efficacy to HU treatment as measured through the the mean change in fetal hemoglobin (between baseline and end of 3 months) and safety, measured as the proportion of participants experiencing serious adverse events related to HU at week 2, 6, 10 and at the end of 3 months. REDCap, an open source software application will be used to collect data using clinical research forms. Conclusion: This project has the potential for the development of novel strategies for improving HU adherence in SCA.

Official Title
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Effect of Mobile-Directly Observed Therapy (DOT) on Adherence to Hydroxyurea Treatment in Adult HbSS Patients at Muhimbili National Hospital (MNH) in Tanzania: a Pilot Study

Conditions
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Sickle Cell Anaemia

Intervention / Treatment
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* Drug: Hydroxyurea
* Device: Mobile Directly Observed Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years and living in urban Dar es Salaam Male or female (post-menopausal, sterile, or using an acceptable method of contraception) Negative urine pregnancy test at Screening and a negative urine pregnancy test (dipstick) prior to randomization and dosing Hemoglobin SS genotype Absolute neutrophil count >1,500/uL Platelet count >95,000/uL Serum creatinine< 100 µmol/L (1.2 mg/dL) Alanine transaminase (ALT) less than two times the upper limit of normal Being able and willing to record and submit videos electronically Exclusion Criteria: Chronic transfusion program as defined by participating in a scheduled (pre-planned) series of transfusions for prophylactic purposes or has a hemoglobin A level that is >20% of the total hemoglobin Hemoglobin <4.0 g/dL HIV positive Female planning to become pregnant during the study period Serious mental (including psychosis) or physical illness, which, in the opinion of the Investigators would compromise participation in the study (e.g. impaired mental capacity, alcoholism Any condition which the Investigators judge to preclude safe participation in the study or to confound the evaluation of the study outcome.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard monitoring (SM) arm<br>Participants will receive fixed dose hydroxyurea therapy (15 mg/Kg/day) with standard monitoring. Standard monitoring is defined as a follow-up visit two weeks after initiation of therapy and monthly follow-ups thereafter | Drug: Hydroxyurea<br>* Patients will receive fixed dose Hydroxyurea therapy (15 mg/Kg/day) with standard monitoring<br>|
| Experimental: mDOT arm<br>Participants will receive fixed dose hydroxyurea therapy (15 mg/Kg/day) and Mobile Directly Observed Therapy (mDOT) consisting of a web based medication adherence monitoring system that includes direct video confirmation of adherence using the patient's personal cellular telephone. Participants will receive alerts on their cell phone at pre-arranged times to remind them to take their medications. Participants will be followed-up at two weeks after initiation of therapy and monthly thereafter. | Drug: Hydroxyurea<br>* Patients will receive fixed dose Hydroxyurea therapy (15 mg/Kg/day) with standard monitoring<br>Device: Mobile Directly Observed Therapy<br>* Mobile DOT will consist of a web based medication adherence monitoring system that includes direct video confirmation of adherence using the patient's personal cellular telephone. Patients will receive alerts on their cell phone at pre-arranged times to remind them to take their medications.<br>* Other names: mDOT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants achieving ≥80% HU adherence as assessed through medication possession ratio. | The proportion of participants achieving ≥80% HU adherence will compared between the two arms. | At the end of 3 months of Hydroxyurea treatment and monitoring. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Hydroxyurea treatment as measured through the mean change in fetal hemoglobin (%), | The mean change in fetal hemoglobin (between baseline and end of 3 months) will be compared between the two arms. | At the end of 3 months of Hydroxyurea treatment and monitoring. | 
| The proportion of participants experiencing serious adverse events related to hydroxyurea |  | at week 2, 6 ,10 and at the end of 3 months of Hydroxyurea treatment and monitoring. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle cell disease, Hydroxyurea, Adherence, randomized trial, medication possession ratio