Exploring Adherence Monitoring in Sickle Cell Disease

• ClinicalTrials.gov Identifier: NCT03708731
• Recruitment Status: Recruiting
• First Posted: October 17, 2018
• Last Update Posted: April 20, 2022
• Sponsor: St. Jude Children's Research Hospital
• Information provided by (Responsible Party): St. Jude Children's Research Hospital

Tracking Information

• First Submitted Date: October 4, 2018
• First Posted Date: October 17, 2018
• Last Update Posted Date: April 20, 2022
• Actual Study Start Date: October 9, 2018
• Estimated Primary Completion Date: June 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 12, 2018)

• Estimate the association between AdhereTech device HU adherence to caregiver-report of adherence [ Time Frame: Continuous over two months, baseline to off study ]
  For each subject, we will calculate the proportion of days of opening the AdhereTech device across the two month study period (days with missing information will not be counted). Caregiver-report of their child's HU adherence will be assessed by the Medical Adherence Measure (MAM), a measure of 7-day self-reported adherence. Each subject's caregiver-reported adherence will be calculated as: [(medication reported taken [(medication reported taken ÷ medication prescribed) x 100]. We will estimate the Spearman's rank-based correlation, with 95% confidence interval, of the AdhereTech device adherence with the caregiver-report of their child's adherence.
• Estimate the association between AdhereTech device HU adherence to youth-reported adherence [ Time Frame: Continuous over two months, baseline to off study ]
  For each subject, we will calculate the proportion of days of opening the AdhereTech device across the two month study period (days with missing information will not be counted). Youth-report of their HU adherence will be assessed by the Medical Adherence Measure (MAM), a measure of 7-day self-reported adherence. Each subject's self-reported adherence will be calculated as: [(medication reported taken [(medication reported taken ÷ medication prescribed) x 100]. We will estimate the Spearman's rank-based correlation, with 95% confidence interval, of the AdhereTech device adherence with the youth-reported adherence.
• Estimate the association between AdhereTech device HU adherence to fetal hemoglobin (HbF) lab values [ Time Frame: Continuous over two months, baseline to off study ]
  For each subject, we will calculate the proportion of days of opening the AdhereTech device across the two month study period (days with missing information will not be counted). We will extract fetal hemoglobin (HbF; g/dl) lab value from each subject's medical record. We will estimate the Spearman's rank-based correlation, with 95% confidence interval, of the AdhereTech device adherence with the fetal hemoglobin (HbF) lab value.
• Estimate the association between AdhereTech device HU adherence to mean corpuscular volume (MCV) lab values [ Time Frame: Continuous over two months, baseline to off study ]
  For each subject, we will calculate the proportion of days of opening the AdhereTech device across the two month study period (days with missing information will not be counted). We will extract mean corpuscular volume (MCV; L) lab value from each subject's medical record. We will estimate the Spearman's rank-based correlation, with 95% confidence interval, of the AdhereTech device adherence with the mean corpuscular volume (MCV) lab value .
• Estimate the association between AdhereTech device HU adherence to the Medication Possession Ratio (MPR) [ Time Frame: Continuous over two months, baseline to off study ]
  For each subject, we will calculate the proportion of days of opening the AdhereTech device across the two month study period (days with missing information will not be counted). Medication Possession Ratio (MPR) will be calculated as: [(number of days medication in family's possession ÷ number of days for which medication prescribed) x 100]. We will estimate the Spearman's rank-based correlation, with 95% confidence interval, of the AdhereTech device adherence with the Medication Possession Ratio (MPR).
• Estimate the association between AdhereTech device HU adherence to pill count [ Time Frame: Continuous over two months, baseline to off study ]
  For each subject, we will calculate the proportion of days of opening the AdhereTech device across the two month study period (days with missing information will not be counted). We will calculate each subject's pill count adherence as: [(number of pills removed ÷ medication prescribed) x 100]. We will estimate the Spearman's rank-based correlation, with 95% confidence interval, of the AdhereTech device adherence with pill count adherence.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 12, 2018)

• Estimate rate of consent to the study [ Time Frame: Once, at baseline ]
  We will descriptively examine rate of refusal and study participation: (Number participants consented ÷ Total families approached) x 100%
• Estimate rate of AdhereTech device use [ Time Frame: Continuous over two months, baseline to off study ]
  We will descriptively examine rate of AdhereTech device use: (Number participants keeping medication in device during entire trial ÷ Total participants) x 100%
• Estimate rate of AdhereTech device failure [ Time Frame: Continuous over two months, baseline to off study ]
  We will descriptively examine AdhereTech device failure (i.e., a device does not register openings as verified by study staff at the time device is returned to study team): (Number devices failing ÷ Total devices) x 100%
• Estimate the perceived acceptability of using the AdhereTech device, as reported by caregivers and youth [ Time Frame: Continuous over two months, baseline to off study ]
  We will descriptively examine reported acceptability of using the AdhereTech device: Point estimation and interval estimations for the counts and frequencies of favorable responses of acceptability will be calculated.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Exploring Adherence Monitoring in Sickle Cell Disease
• Official Title: Exploring Adherence Monitoring in Sickle Cell Disease

Brief Summary

Despite the well-documented benefits of hydroxyurea (HU) therapy in decreasing morbidity and mortality in youth with Sickle cell disease (SCD), pediatric HU adherence rates range as low as 49% and lead to discontinuation of HU regimens in 8-20%. In addition, treatment non-adherence may lead to unnecessary increases in medication dosage resulting from erroneous assumption that a patient is non-responsive to treatment (versus non-adherent to the regimen as prescribed). Given the detrimental effects of non-adherence, assessment of and intervention for HU non-adherence is essential to improving health outcomes in the pediatric SCD population.

Electronic adherence monitoring is widely considered the "gold standard" in objective adherence measurement. These monitors provide continuous, real- time records of medication adherence and reveal problematic behavior patterns, including underdosing, overdosing, delayed dosing, "drug holidays," and "white coat" adherence. Overall, electronic adherence measures are considered valid, reliable, and accurate, with clear advantages over pharmacy refill records, physician estimates and self-report measures.

The primary purpose of this pilot study is to determine the use of the AdhereTech as a feasible and valid measure of HU adherence in pediatric SCD.

Primary Objective Estimate the association between HU adherence as measured by the AdhereTech device to a) caregiver-report, b) youth-report, c) lab values, d) pill- count, and e) Medication Possession Ratio (MPR) adherence measures Secondary Objectives Estimate the rate of consent to the study, the rate of AdhereTech device use, the rate of AdhereTech device failure, and the perceived acceptability of using the AdhereTech device, as reported by caregivers and youth

Detailed Description

The AdhereTech smart bottle is an electronic medicine dispenser with a tracking and reminder system connected wirelessly. The device provides real time adherence aids to the patient and this information is relayed to the provider. The device can sense the amount of pills remaining inside the bottle. This information is measured periodically and concurrently sent to a secure database using cellular data technology. Thus, AdhereTech bottles can be used to determine whether medication was removed from the bottle, the amount of medication removed, and the timing of removal.

Participants ages 12.0-17.99 who are receiving HU prescribed in pill form will use the AdhereTech smart bottle for a two-month period. Participants and their caregivers will complete self-report measures of adherence at the baseline, 1 month and 2 month clinic visits, a Demographic questionnaire at the baseline clinic visit and an Acceptability questionnaire at the 1 month and 2 month clinic visits using Audio Computer-Assisted Self-Interviews (ACASI) on a password protected laptop.

Lab values and clinical information will be obtained through medical records review and adherence information from pill counts and pharmacy records.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Participants ages 12.0-17.99 with Sickle cell disease any genotype and their caregivers
• Condition: Sickle Cell Disease
• Intervention: Not Provided

Study Groups/Cohorts

Sickle Cell Disease

All participants who meet eligibility requirements and consent to the study.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 12, 2018): 45
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 31, 2025
• Estimated Primary Completion Date: June 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Confirmed diagnosis of SCD (any genotype)
• Ages 12.0 - 17.99 at time of study enrollment
• Stable HU dose composed of only one capsule strength prescribed in pill formulation for ≥ 6 months without documented hematological toxicity (excluding dose adjustments for weight gain)
• Lives with their legal guardian
• Anticipated to return to clinic at proposed 4-week intervals

Exclusion Criteria:

• Primary caregiver and/or youth unable to understand English and/or youth not cognitively intact (known IQ < 70) such that the study questionnaire cannot be understood and completed.
• Participant unable to complete the questionnaires due to refusal or current acute illness (e.g., pain crisis).
• Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Jerlym Porter, PhD; 866-278-5833; referralinfo@stjude.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03708731
• Other Study ID Numbers: ExAMS
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: St. Jude Children's Research Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: St. Jude Children's Research Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jerlym Porter, PhD; St. Jude Children's Research Hospital

• PRS Account: St. Jude Children's Research Hospital
• Verification Date: April 2022