Clinical trial NCT02844673: Mobile-Directly Observed Therapy on Adherence to Hydroxyurea
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle Cell Anaemia
Keywords: Sickle cell disease
Hydroxyurea
Adherence
randomized trial
medication possession ratio
Lead sponsor: Muhimbili University of Health and Allied Sciences
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh
name: Muhimbili National Hospital
First posted: 2016-07-26
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The proportion of participants achieving ≥80% HU adherence as assessed through medication possession ratio.
timeFrame: At the end of 3 months of Hydroxyurea treatment and monitoring.
Secondary outcomes:
measure: Efficacy of Hydroxyurea treatment as measured through the mean change in fetal hemoglobin (%),
timeFrame: At the end of 3 months of Hydroxyurea treatment and monitoring.
measure: The proportion of participants experiencing serious adverse events (SAE) related to hydroxyurea
timeFrame: at week 2, 6 ,10 and at the end of 3 months of Hydroxyurea treatment and monitoring.
Other outcomes:
measure: Incidence of laboratory adverse events, fever and other sickle cell anemia symptoms
timeFrame: At the end of 3 months Hydroxyurea treatment and monitoring
measure: Level of leucopenia in relation to incidence rates of fever as indicator of possible infection
timeFrame: At the end of 3 months Hydroxyurea treatment and monitoring
measure: Mean change in estimated glomerular filtration rate as a measure of kidney function
timeFrame: At the end of 3 months Hydroxyurea treatment and monitoring
measure: Mean change in the level of Lactate Dehydrogenase (LDH) from baseline
timeFrame: At the end of 3 months Hydroxyurea treatment and monitoring
measure: Mean change in reticulocyte count from baseline
timeFrame: At the end of 3 months Hydroxyurea treatment and monitoring
Locations:
city: Dar es Salaam
country: Tanzania
facility: Muhimbili University of Health and Allied Sciences
Study officials:
affiliation: Muhimbili University of Health and Allied Sciences
name: Julie Makani, PhD
role: STUDY_CHAIR
affiliation: Muhimbili University of Health and Allied Sciences
name: Abel Makubi, MMed
role: PRINCIPAL_INVESTIGATOR
affiliation: Muhimbili University of Health and Allied Sciences
name: Philip Sasi, PhD
role: STUDY_DIRECTOR
References:
citation: 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.