Clinical trial NCT04080167: Integration of mHEALTH Into the Care of Patients With Sickle Cell Disease to Increase Hydroxyurea Utilization
Official title: Integration of mHEALTH Into the Care of Patients With Sickle Cell Disease to Increase Hydroxyurea Utilization- mESH Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sickle Cell Disease
Keywords: implementation science
sickle cell anemia
digital medicine
adherence
hydroxycarbamide
health innovation
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: RTI International
name: National Heart, Lung, and Blood Institute (NHLBI)
name: University of Memphis
First posted: 2019-09-06
Enrollment: 382
Sex: ALL
Minimum age (years): 15
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: nonrandomized, closed cohort, stepped-wedge cluster trial
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: This project proposes to develop, test and evaluate targeted interventions to improve clinical provider prescribing of and patient adherence to hydroxyurea (HU). Using a stepped-wedge design, The investigators will test two innovative interventions utilizing mobile health to address both patients' and providers' needs: 1) an mHealth application for patients (InCharge Health app) that includes multi-component features to address the memory, motivation, and knowledge barriers to hydroxyurea use, and 2) an mHealth toolbox application for providers (HU Toolbox app) that addresses clinical knowledge barriers in prescribing and monitoring hydroxyurea use. These two interventions will be tested through the following aims:

Aim 1. Improve Patient Adherence to Hydroxyurea: Addressing Memory, Motivation, and Knowledge Barriers to Hydroxyurea Use. Primary hypothesis: The investigators hypothesize that among adolescents and adults with SCD, the adherence to hydroxyurea, as measured by percentage of days covered (PDC), will increase by at least 20% at 24 weeks after receiving the InCharge Health app, compared to their hydroxyurea adherence at baseline.

Sub-aim 1.a. To examine and assess both patient engagement and behaviors related to use of the InCharge Health app, the investigators will evaluate consistent use of the app among enrolled patients, patient satisfaction, and continued use of the app beyond the study period.

Sub-Aim 1.b. To examine the clinical influence of the use of the InCharge Health app on PDC, patients' clinical outcomes, perceived health literacy, health related quality of life, and perceived self-efficacy between baseline and 24 weeks.

Aim 2. Improve Provider Hydroxyurea Awareness, Prescribing and Monitoring Behaviors.

Sub-Aim 2.a. To examine and assess provider engagement and behaviors related to use of the HU Toolbox, the investigators will evaluate consistent use of the app among enrolled providers, providers' satisfaction, and continued use of the app beyond the study period.

Sub-Aim 2.b. To assess the combined effects of the patient and provider mHealth interventions on hydroxyurea and health care utilization, the investigators will examine if the changes in hydroxyurea adherence are enhanced by the use of both provider and patient interventions compared to those not exposed to one or both interventions.

Aim 3. Identify and Evaluate the Barriers and Facilitators to the use of mHealth Interventions.

Detailed description: The National Heart, Lung, and Blood Institute (NHLBI) created the Sickle Cell Disease Implementation Consortium (SCDIC) to apply implementation science methods to identify and address barriers to guideline-based care in sickle cell disease (SCD) and promote evidence-based treatment for SCD patients between ages 15 to 45 years. The SCDIC conducted a systematic literature review and a comprehensive needs assessment among the eight participating centers. A major conclusion was that care redesign to support better hydroxyurea utilization would likely improve clinical outcomes for patients with SCD. Hydroxyurea therapy has been shown to improve patient outcomes and reduce disease complications and is endorsed by the NHLBI. SCDIC now proposes to develop, test and evaluate targeted interventions to improve clinical provider prescribing of and patient adherence to hydroxyurea.

The overall purpose of this proposed project is to address barriers identified by the needs assessment to improve adherence with hydroxyurea therapy. Multiple approaches for improving adherence with pharmaceutical regimens have been studied and demonstrate a need to address barriers that both providers and patients face. This project aims, via a stepped-wedge design, to test two innovative interventions utilizing mobile health (mHealth), to address both patients' and providers' needs: 1) an mHealth application for patients (InCharge Health app) that includes multi-component features to address the memory, motivation, and knowledge barriers to hydroxyurea use, and 2) an mHealth toolbox application for providers (HU Toolbox app) that addresses the clinical knowledge barriers in prescribing and monitoring hydroxyurea use. These two interventions will be tested through the following aims:

Aim 1. Improve Patient Adherence to Hydroxyurea: Addressing Memory, Motivation, and Knowledge Barriers to Hydroxyurea Use. Primary hypothesis: The investigators hypothesize that among adolescents and adults with SCD, the adherence to hydroxyurea, as measured by percentage of days covered (PDC), will increase by at least 20% at 24 weeks after receiving the InCharge Health app, compared to their hydroxyurea adherence at baseline.

Sub-aim 1.a. To examine and assess both patient engagement and behaviors related to use of the InCharge Health app, the investigators will evaluate consistent use of the app among enrolled patients, patient satisfaction, and continued use of the app beyond the study period.

Sub-Aim 1.b. To examine the clinical influence of the use of the InCharge Health app on PDC, patients' clinical outcomes, perceived health literacy, health related quality of life, and perceived self-efficacy between baseline and 24 weeks.

Aim 2. Improve Provider Hydroxyurea Awareness, Prescribing and Monitoring Behaviors. The investigators will examine among providers using the HU Toolbox App if there is an increase in reported awareness of hydroxyurea benefits and risks, accurate prescribing of hydroxyurea, and perceived self-efficacy to correctly administer hydroxyurea therapy between baseline and after 9 months of using the HU Toolbox app.

Sub-Aim 2.a. To examine and assess provider engagement and behaviors related to use of the HU Toolbox, the investigators will evaluate consistent use of the app among enrolled providers, providers' satisfaction, and continued use of the app beyond the study period.

Sub-Aim 2.b. To assess the combined effects of the patient and provider mHealth interventions on hydroxyurea and health care utilization, the investigators will examine if the changes in hydroxyurea adherence are enhanced by the use of both provider and patient interventions compared to those not exposed to one or both interventions.

Aim 3. Identify and Evaluate the Barriers and Facilitators to the use of mHealth Interventions. The investigators will evaluate the strategies used by participating sites in supporting the implementation of mHealth interventions via a mixed-method evaluation of the facilitators and barriers in adopting and implementing the mHealth interventions from multiple stakeholder perspectives: patient, provider, and organization.

Both mHealth interventions will be tested concurrently and because the investigators are using a stepped-wedge design, each site will enter the study at different times. Provider participants will receive the HU Toolbox intervention for 9 months with a lagged but overlapping introduction of the InCharge Health intervention patient participants for 24 weeks. The implementation evaluation will be guided by RE-AIM to assess the Reach, Effectiveness, Adoption, Implementation and Maintenance of the interventions. All sites will also complete follow-on needs assessment and medical record abstractions that will provide data to evaluate other patient and provider outcomes, barriers and enablers to hydroxyurea prescribing, use, and monitoring.

mHealth technology can be leveraged to support more effective use of hydroxyurea and eventually improved SCD clinical outcomes. If the mHealth applications tested in this study show preliminary efficacy, both apps could be scaled up within SCDIC centers and expanded to other institutions outside the SCDIC.

Eligibility criteria: Inclusion Criteria:

* Age 15 years up to and including 45 years
* Treated at or affiliated with one of the SCDIC sites
* English speaking
* Confirmed Sickle Cell Disease (SCD) diagnosis. An SCD diagnosis is defined as Hb fractionation test (e.g., high- performance liquid chromatography or another technique) that is diagnostic of one the following: Hb SS, Hb SC, Hb Sβ-thalassemia, Hb SO, Hb SD, Hb SG, Hb SE, or Hb SF.
* Willing and cognitively able to give informed consent
* Access to a cellular/mobile smart phone (either Android or IPhone are acceptable)
* Hydroxyurea therapy: Already receiving hydroxyurea therapy: defined as at least one prior prescription to hydroxyurea in the past 3 months and no plans to escalate the dose by more than 5 mg/kg/day. Initiating hydroxyurea therapy: defined as at least one prescription written at the time of study enrollment (the first prescription must be written on the same day as study enrollment). Patients who initiate hydroxyurea on the same day of study enrollment will not contribute to the total of 46 patients target accrual for the site. A max of 30 patients who are initiating hydroxyurea can be enrolled per site.

Exclusion Criteria:

* Current pregnancy
* On a chronic transfusion program in which they receive more than 8 erythrocyte transfusions in a 12-month period.
* A red blood cell transfusion in the past 60 days
* Currently using another phone application or an online-based tool (e-health tool) to increase hydroxyurea adherence

Primary outcomes:
measure: Mean Change in PDC From Baseline Through 24 Weeks
timeFrame: baseline (prior to the intervention), week 24
Secondary outcomes:
measure: Implementation of InCharge Health App.
timeFrame: baseline, 24 weeks
measure: Change in Mean Corpuscular Volume (MCV)
timeFrame: baseline, 24 weeks
measure: Change in Fetal Hemoglobin
timeFrame: baseline, 24 weeks
measure: Change in Hemoglobin Concentration
timeFrame: baseline, 24 weeks
measure: Change in Reticulocyte Percentage
timeFrame: baseline, 24 weeks
measure: Change in Absolute Neutrophil Percentage
timeFrame: baseline, 24 weeks
measure: Change Bilirubin
timeFrame: baseline, 24 weeks
measure: Change in Mean Plasma Lactate Dehydrogenase (LDH)
timeFrame: baseline, 24 weeks
measure: Change in Rate of Emergency Room Visits Per Patient in the Last 24 Weeks
timeFrame: baseline, 24 weeks
measure: Change in Rate of Hospitalization Per Patient in the Last 24 Weeks
timeFrame: baseline, 24 weeks
measure: Change in Patient Reported Pain Quality
timeFrame: baseline, 24 weeks
measure: Change in Patient Reported Pain Impact: ASCQ-Me Pain Impact Scale
timeFrame: baseline, 24 weeks
measure: Change in Patient Reported Pain Frequency and Severity
timeFrame: baseline, 24 weeks
measure: Change in Healthy Literacy
timeFrame: baseline, 24 weeks
measure: Change in Perceived Self-efficacy
timeFrame: baseline, 24 weeks
measure: Change in Provider Knowledge of Hydroxyurea (HU) Prescription Guidelines
timeFrame: baseline, 9 months
measure: Change is Provider Self-efficacy of Hydroxyurea (HU) Prescription Guidelines
timeFrame: baseline, 9 months
measure: Mean Change in PDC From Baseline Through 36 Weeks
timeFrame: baseline (prior to the intervention), week 36
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Georgia Regents University
state: Georgia
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Jane Hankins, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Badawy SM, DiMartino L, Brambilla D, Klesges L, Baumann A, Burns E, DeMartino T, Jacobs S, Khan H, Nwosu C, Shah N, Hankins JS; Sickle Cell Disease Implementation Consortium. Impact of the COVID-19 Pandemic on the Implementation of Mobile Health to Improve the Uptake of Hydroxyurea in Patients With Sickle Cell Disease: Mixed Methods Study. JMIR Form Res. 2022 Oct 14;6(10):e41415. doi: 10.2196/41415.
citation: Hankins JS, Shah N, DiMartino L, Brambilla D, Fernandez ME, Gibson RW, Gordeuk VR, Lottenberg R, Kutlar A, Melvin C, Simon J, Wun T, Treadwell M, Calhoun C, Baumann A, Potter MB, Klesges L, Bosworth H; Sickle Cell Disease Implementation Consortium. Integration of Mobile Health Into Sickle Cell Disease Care to Increase Hydroxyurea Utilization: Protocol for an Efficacy and Implementation Study. JMIR Res Protoc. 2020 Jul 14;9(7):e16319. doi: 10.2196/16319.