Integration of mHEALTH Into the Care of Patients With Sickle Cell Disease to Increase Hydroxyurea Utilization

Sickle Cell Disease Clinical Trial

Official title:

Integration of mHEALTH Into the Care of Patients With Sickle Cell Disease to Increase Hydroxyurea Utilization- mESH Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04080167
• Other study ID #: mESH
• Secondary ID: 5U01HL133996
• Status: Completed
• Phase: N/A
• Start date: November 11, 2019
• Est. completion date: August 31, 2022

Study information

• Verified date: November 2023
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 382
• Est. completion date: August 31, 2022
• Est. primary completion date: April 6, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 15 Years to 45 Years

Eligibility

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 Sß-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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Behavioral:
• InCharge Health mobile application
The InCharge Health app features include: Daily reminders; Ability to customize content of message and time of day when the message comes; Symptom tracker to monitor daily pain and mood; 7-day streak that tracks daily adherence; Graphing adherence against pain symptoms; Communication feature allowing the patient to connect to the clinic and a "health partner"; Link to discussion forum where communication to other patients can occur; Education bank that provides information about SCD and hydroxyurea. Participants can delay daily push notifications. If hospitalized, participants may stop notifications. A special feature of the app is to set up a "health partner", who may be a person the participant may choose from his/her contact list and who will receive notifications if it had been <4 hours since not documenting the use of hydroxyurea. The "app healthy partner" will be encouraged to message the participant to remind him/her to take the medication.
• HU Toolbox mobile application
The HU Toolbox app includes algorithms for hydroxyurea use and is ready for immediate use on Apple and Android operating systems. In addition, it has the NHLBI guidelines adapted for pediatrics (guidelines/recommendations separated by age) and for adults (guidelines/ recommendations separated by organ system, laboratory, or physical exam finding). The HU Toolbox app includes the ability to search guidelines for key words and add notes. Algorithms are also included as PDF documents that can be printed out or emailed. Finally, a contact list of local SCD specialists and important contacts is included, so providers can easily contact SCD experts and expect an answer in 24 hours or less. The HU Toolbox app is easily updated with all data and resources stored on a cloud-based server that can provide instant up-to-date information to those using the app.

Locations

Country	Name	City	State
United States	Georgia Regents University	Augusta	Georgia
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Illinois	Chicago	Illinois
United States	Duke University	Durham	North Carolina
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Washington University	Saint Louis	Missouri

Sponsors (4)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	National Heart, Lung, and Blood Institute (NHLBI), RTI International, University of Memphis

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change in PDC From Baseline Through 24 Weeks	The primary outcome is the change in the percentage of days covered (PDC) of hydroxyurea, measured by comparing PDC during the 24-week baseline interval (i.e. prior the intervention) with PDC during the 24-week follow-up interval. PDC is calculated as the number of days covered (i.e., days of prescription refill dates and supply of each prescription) divided by the number of days in a treatment time point then multiply by 100 to obtain the PDC as a percentage.	baseline (prior to the intervention), week 24
Secondary	Implementation of InCharge Health App.	Count of all enrolled patients who used the InCharge Health app at least once during the study period among all enrolled	baseline, 24 weeks
Secondary	Change in Mean Corpuscular Volume (MCV)	Mean difference between MCV during the baseline interval and during the follow-up interval	baseline, 24 weeks
Secondary	Change in Fetal Hemoglobin	Mean difference between fetal hemoglobin during the baseline interval and during the follow-up interval	baseline, 24 weeks
Secondary	Change in Hemoglobin Concentration	Mean difference between hemoglobin during the baseline interval and during the follow-up interval	baseline, 24 weeks
Secondary	Change in Reticulocyte Percentage	Mean difference between reticulocyte percentage during the baseline interval and during the follow-up interval	baseline, 24 weeks
Secondary	Change in Absolute Neutrophil Percentage	Mean difference between neutrophil percentage during the baseline interval and during the follow-up interval	baseline, 24 weeks
Secondary	Change Bilirubin	Mean difference between total bilirubin during the baseline interval and during the follow-up interval	baseline, 24 weeks
Secondary	Change in Mean Plasma Lactate Dehydrogenase (LDH)	Mean difference between LDH during the baseline interval and during the follow-up interval	baseline, 24 weeks
Secondary	Change in Rate of Emergency Room Visits Per Patient in the Last 24 Weeks	Mean difference between number of emergency room visits during the baseline interval and during the follow-up interval.	baseline, 24 weeks
Secondary	Change in Rate of Hospitalization Per Patient in the Last 24 Weeks	Mean difference between number of hospitalizations during the baseline interval and during the follow-up interval.	baseline, 24 weeks
Secondary	Change in Patient Reported Pain Quality	Mean difference between scores on the Patient Reported Outcomes Information System (PROMIS) Pain Quality Scale during baseline and follow-up when the responses, never, rarely, sometimes, often, and always are coded 0 through 4. The Patient Reported Outcomes Information System (PROMIS) Pain Quality Scale has a minimum value of "never", coded as 0, and a maximum value of "always", coded as 4 for analysis. A higher score indicates worse pain.	baseline, 24 weeks
Secondary	Change in Patient Reported Pain Impact: ASCQ-Me Pain Impact Scale	Mean difference between scores on the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) Pain Episode Frequency and Severity Scale during baseline and follow-up when the responses, never, rarely, sometimes, often, and always are coded 0 through 4. Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) Pain Episode Frequency and Severity Scale has a minimum value of "never", coded as 0, and a maximum value of "always", coded as 4 for analysis. A higher score indicates worse pain.	baseline, 24 weeks
Secondary	Change in Patient Reported Pain Frequency and Severity	Mean difference between scores on the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) Pain Episode Frequency and Severity scale during baseline and follow-up when the responses, never, rarely, sometimes, often, and always are coded 0 through 4. Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) Pain Episode Frequency and Severity Scale has a minimum value of "never", coded as 0, and a maximum value of "always", coded as 4 for analysis. A higher score indicates worse pain.	baseline, 24 weeks
Secondary	Change in Healthy Literacy	Mean difference between responses to the Single item literacy screener (SILS) during baseline and follow-up when the responses, Never, rarely, sometimes, often, and always are coded 0 through 4; score is the sum of responses to 8 questions (score range: 0-32). The Single item literacy screener (SILS) has a minimum value of "never", coded as 0, and a maximum value of "always", coded as 4 for analysis. A higher score means lower health literacy.	baseline, 24 weeks
Secondary	Change in Perceived Self-efficacy	Mean difference between responses to the Patient reported outcomes information system (PROMIS) medication self-efficacy short form during baseline and follow-up when the responses, I am not at all confident, I am a little confident, I am somewhat confident, I am quite confident, and I am very confident are coded 0 to 4. The Patient Reported Outcomes Information System (PROMIS) Pain Quality Scale has a minimum value of "I am not at all confident", coded as 0, and a maximum value of "I am very confident", coded as 4 for analysis. A higher score indicates greater self-efficacy.	baseline, 24 weeks
Secondary	Change in Provider Knowledge of Hydroxyurea (HU) Prescription Guidelines	Mean difference between responses during baseline and follow-up to the 5 questions on the Hydroxyurea Knowledge Scale regarding knowledge of correctly prescribing hydroxyurea. Each question was scored 0 (incorrect response) or 1 (correct) and the 5 scores were summed to produce totals of 0 to 5.	baseline, 9 months
Secondary	Change is Provider Self-efficacy of Hydroxyurea (HU) Prescription Guidelines	Hydroxyurea self-efficacy scale (comfort level and perceived effectiveness in prescribing hydroxyurea) with responses scored 0 to 4. The Hydroxyurea self-efficacy scale has a minimum value of "very uncomfortable", coded as 0 and a maximum value of "very comfortable", coded as 4. A higher score indicates greater self-efficacy.	baseline, 9 months
Secondary	Mean Change in PDC From Baseline Through 36 Weeks	This outcome is the change in the percentage of days covered (PDC) of hydroxyurea, measured by comparing PDC during the 24-week baseline interval (i.e. prior the intervention) with PDC during the 36-week follow-up interval. PDC is calculated as the number of days covered (i.e., days of prescription refill dates and supply of each prescription) divided by the number of days in a treatment time point then multiply by 100 to obtain the PDC as a percentage.	baseline (prior to the intervention), week 36

External Links

•   ClinicalTrials Open at St. Jude
•   St. Jude Children's Research Hospital