Mobile-Directly Observed Therapy on Adherence to Hydroxyurea (mDOT)

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

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.

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.

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

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.

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.

The proportion of participants achieving ≥80% HU adherence as assessed through medication possession ratio.

The mean change in fetal hemoglobin (between baseline and end of 3 months) will be compared between the two arms.

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.

Yes, investigators plan to share the database with one of the collaborators, University of Pittsburgh, USA

Makubi A, Sasi P, Ngaeje M, Novelli EM, Mmbando BP, Gladwin MT, Makani J. Rationale and design of mDOT-HuA study: a randomized trial to assess the effect of mobile-directly observed therapy on adherence to hydroxyurea in adults with sickle cell anemia in Tanzania. BMC Med Res Methodol. 2016 Oct 18;16(1):140. doi: 10.1186/s12874-016-0245-9.