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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Anaemia
• Intervention / Treatment: Drug: Hydroxyurea; Device: Mobile Directly Observed Therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2

Contacts and Locations

Study Locations

• Tanzania
  • Dar es Salaam, Tanzania, 11101
    • Muhimbili University of Health and Allied Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard monitoring (SM) arm; 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; Patients will receive fixed dose Hydroxyurea therapy (15 mg/Kg/day) with standard monitoring
Experimental: mDOT arm; 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; Patients will receive fixed dose Hydroxyurea therapy (15 mg/Kg/day) with standard monitoring; Device: Mobile Directly Observed Therapy; 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.; Other Names: mDOT

What is the study measuring?

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 (SAE) related to hydroxyurea	The overall proportion of participants experiencing SAE during the 3 months of Hydroxyurea treatment will be evaluated as a measure of the safety of treatment with Hydroxyurea	at week 2, 6 ,10 and at the end of 3 months of Hydroxyurea treatment and monitoring.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of laboratory adverse events, fever and other sickle cell anemia symptoms	The incidence during 3 months of treatment will be compared with the incidence during pre-treatment period	At the end of 3 months Hydroxyurea treatment and monitoring
Level of leucopenia in relation to incidence rates of fever as indicator of possible infection	The level of leucopenia in relation to incidence rate of fever during 3 months of treatment with be compared with that during the pre-treatment period	At the end of 3 months Hydroxyurea treatment and monitoring
Mean change in estimated glomerular filtration rate as a measure of kidney function	The mean change in estimated glomerular filtration rate will be evaluated as an indicator of deteriorating renal function after Hydroxyurea exposure	At the end of 3 months Hydroxyurea treatment and monitoring
Mean change in the level of Lactate Dehydrogenase (LDH) from baseline	Serum LDH level (U/L) is usually elevated in sickle cell anemia indicating hemolysis. A decrease in the level of LDH will be considered favorable effect of Hydroxyurea	At the end of 3 months Hydroxyurea treatment and monitoring
Mean change in reticulocyte count from baseline	Reticulocyte count is usually increased in sickle cell anemia, indicating of hemolysis (a decrease in reticulocyte count % will be considered favorable effect of Hydroxyurea)	At the end of 3 months Hydroxyurea treatment and monitoring

Collaborators and Investigators

• Sponsor: Muhimbili University of Health and Allied Sciences
• Collaborators: University of Pittsburgh; Muhimbili National Hospital
• Investigators: Study Chair: Julie Makani, PhD, Muhimbili University of Health and Allied Sciences; Principal Investigator: Abel Makubi, MMed, Muhimbili University of Health and Allied Sciences; Study Director: Philip Sasi, PhD, Muhimbili University of Health and Allied Sciences

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2017
• Primary Completion (Actual): January 28, 2018
• Study Completion (Actual): May 18, 2018

Study Registration Dates

• First Submitted: July 18, 2016
• First Submitted That Met QC Criteria: July 21, 2016
• First Posted (Estimated): July 26, 2016

Study Record Updates

• Last Update Posted (Actual): June 12, 2024
• Last Update Submitted That Met QC Criteria: June 8, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Adherence; randomized trial; Hydroxyurea; Sickle cell disease; medication possession ratio
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antisickling Agents; Hydroxyurea
• Other Study ID Numbers: MUPI-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Yes, investigators plan to share the database with one of the collaborators, University of Pittsburgh, USA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No