Sickle Cell Disease
Conditions
Keywords
Hydroxyurea, Community health worker (CHW), Text messages, Medication adherence
Brief summary
Many youth with chronic disease have difficulty taking medication every day and therefore do not receive full benefit from treatment. Sickle Cell Disease (SCD) is an inherited blood disease that affects African Americans and other underserved communities. Hydroxyurea (HU) is the sole FDA-approved drug therapy for SCD and is highly effective and improves quality of life. The proposed study, a 5-site four-year randomized control trial (RCT), builds upon the investigators' recent feasibility study of the same title. Overall goals are reducing barriers to HU use and improving adherence for youth 10-18 years through creation of a daily medication habit. The goal of the proposed multi-site study is to test the efficacy of the HABIT intervention at 6 months and sustainability of the effect at 12 months.
Detailed description
Barriers to medication adherence are common in youth with chronic illness and are a source of racial/ethnic disparities in underserved communities. An inherited blood disease, Sickle Cell Disease (SCD) is characterized by chronic and acute illness and reduced quality of life (QOL). It affects African Americans and other underserved communities. Hydroxyurea (HU) is the sole FDA-approved drug therapy for SCD and is highly effective and improves QOL. Poor adherence is common among youth and young adults with SCD. The importance of poor medication adherence, use of community-based health workers (CHWs) to bridge the gap between health services and underserved parent-youth dyads affected by SCD, the strength of the science, the success of the investigators' multi-ethnic feasibility study, and the potential application of study findings to youth with other serious chronic illnesses speak to the importance of this trial.
Interventions
BEHAVIORALHABIT Intervention
Dyads randomized to the intervention group will receive the HABIT intervention, which includes CHW support and tailored text messages.
OTHERStandard of Care
Standard of care used to treat patients with SCD
OTHEREducation materials
Education materials provided to all patients enrolled in the trial
Sponsors
National Institute of Nursing Research (NINR)
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
- Youth: * One of the two most common sickle cell disease variants (HbSS or HbS-B0 thalassemia) * Age 10 through18 years (inclusive) * Currently prescribed hydroxyurea (HU) ≥18 months (for identifying historical Personal best HbF) * Current HU dose is within 5% of dose at Personal Best HbF * Pre-enrollment HbF ≥15% below historical Personal best, based on mean of ≥2 HbF assessments over preceding 12 months * Youth able to speak/read English or Spanish Inclusion Criteria - Parent: * Parent/guardian speaks/reads English or Spanish * Parent/ legal guardian willing to participate * Family expects to reside in community for ≥ 1.5 years
Exclusion criteria
- Youth: * Youth not prescribed HU * \<2 HbF assessments over past 12 months * Transfusion within 3 months preceding enrollment * Final screen HbF (visit 0) of ≤15% decrease below Personal best HbF * Sexually active female 10 years or older and not using reliable contraception (due to HU teratogenic risk) * Pregnancy * Cognitive impairment (\>2 levels below expected grade) * Youth not residing with parent/legal guardian
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Biomarker Fetal Hemoglobin (HbF) | Baseline, 6 months, 12 months | A serum biomarker obtained from youth used to measure adherence to hydroxyurea |
| Mean Change in Proportion of Days Covered (PDC) by Hydroxyurea | Baseline, 6 months, 12 months | The days covered by hydroxyurea was assessed using youth prescription refill data and was used to measure hydroxyurea adherence. The baseline measure is the proportion of days covered by hydroxyurea in the year prior to study enrollment, using prescription refill data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Youth Score on Peds Quality of Life (Generic Quality of Life) | Baseline, 4 months, 9 months and 12 months | Used to measure health-related quality of life. Scores range from 0-100 with a higher score indicating a better quality of life. |
| Mean Change in Youth Score on PedsQL Sickle Cell Disease Module (Disease Specific Quality of Life) | Baseline, 9 months and 12 months | Used to measure sickle cell disease specific health-related quality of life. Scores range from 0-100 with a higher score indicating a better quality of life. |
| Mean Change in Parent Youth Concordance Regarding Self-management Responsibility | Baseline, 6 months and 12 months | Concordance between parent and youth scores Sickle Cell Family Responsibility scores for 11 items measuring self-management tasks. Scores range from 0-11 with a higher score indicating better concordance. |
Countries
United States
Participant flow
Pre-assignment details
24 Dyads were randomized to the intervention (24 parents + 24 youth) 26 Dyads were randomized to the control (26 parents + 26 youth)
Participants by arm
| Arm | Count |
|---|---|
| Intervention Group In addition to standard care and education handouts, dyads randomized to the intervention group will receive the HABIT intervention, which includes CHW support and tailored text messages. | 24 |
| Control Group Dyads randomized to the control group will receive:
Standard care and Education handouts. | 26 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Intervention Group | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 14.1 years STANDARD_DEVIATION 1.9 | 13.0 years STANDARD_DEVIATION 1.7 | 13.3 years STANDARD_DEVIATION 1.9 |
| Biomarker Fetal Hemoglobin (HbF) | 12.2 Percent STANDARD_DEVIATION 5.9 | 12.4 Percent STANDARD_DEVIATION 5.3 | 12.3 Percent STANDARD_DEVIATION 5.5 |
| Caregiver affected by SCD | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 21 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Had 1 more hospitalizations in past year | 11 Participants | 11 Participants | 22 Participants |
| Had 1 or more ED visits in past year | 11 Participants | 10 Participants | 21 Participants |
| No other chronic condition besides Sickle Cell Disease (SCD) | 12 Participants | 13 Participants | 25 Participants |
| Other people in home affected by SCD | 4 Participants | 6 Participants | 10 Participants |
| Parent education high school or less | 7 Participants | 14 Participants | 21 Participants |
| Parent status: Single, separated or divorced | 16 Participants | 16 Participants | 32 Participants |
| Proportion of days covered by hydroxyurea | 55.2 Percent of days STANDARD_DEVIATION 26.7 | 55.9 Percent of days STANDARD_DEVIATION 26.1 | 55.6 Percent of days STANDARD_DEVIATION 26.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 20 Participants | 41 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 24 participants | 26 participants | 50 participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 12 Participants | 15 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 24 |
| other Total, other adverse events | 0 / 26 | 0 / 24 |
| serious Total, serious adverse events | 0 / 26 | 0 / 24 |
Outcome results
Primary
Mean Change in Biomarker Fetal Hemoglobin (HbF)
A serum biomarker obtained from youth used to measure adherence to hydroxyurea
Time frame: Baseline, 6 months, 12 months
Population: Change between 6-12 months: 22 of 24 intervention group participants analyzed as blood samples were collected at both timepoints for 22 of 24 participants, due to difficulties coming into clinic during the COVID-19 pandemic.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention Group | Mean Change in Biomarker Fetal Hemoglobin (HbF) | Month 6 to Month 12 | -1.7 Percent fetal hemoglobin | Standard Deviation 1.2 |
| Intervention Group | Mean Change in Biomarker Fetal Hemoglobin (HbF) | Baseline to Month 6 | 2.7 Percent fetal hemoglobin | Standard Deviation 1.3 |
| Control Group | Mean Change in Biomarker Fetal Hemoglobin (HbF) | Baseline to Month 6 | 0.3 Percent fetal hemoglobin | Standard Deviation 1.3 |
| Control Group | Mean Change in Biomarker Fetal Hemoglobin (HbF) | Month 6 to Month 12 | 1.8 Percent fetal hemoglobin | Standard Deviation 1.3 |
Comparison: Based on estimated effect size from our prior feasibility trial, the target enrollment was 87 dyads plus additional 20% to account for attrition before Month 6 or blood transfusions or acute illness rendering HbF levels inaccurate.p-value: 0.067Regression, Linear
Primary
Mean Change in Proportion of Days Covered (PDC) by Hydroxyurea
The days covered by hydroxyurea was assessed using youth prescription refill data and was used to measure hydroxyurea adherence. The baseline measure is the proportion of days covered by hydroxyurea in the year prior to study enrollment, using prescription refill data.
Time frame: Baseline, 6 months, 12 months
Population: 21 of 24 intervention group participants and 22 of 26 control group participants analyzed as data could not be collected from pharmacies due to COVID-19 difficulties and loss of data resulting from fire.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention Group | Mean Change in Proportion of Days Covered (PDC) by Hydroxyurea | Baseline and 6 months | 17.9 change in percentage of PDC | Standard Deviation 27.3 |
| Intervention Group | Mean Change in Proportion of Days Covered (PDC) by Hydroxyurea | 6 months and 12 months | -1.6 change in percentage of PDC | Standard Deviation 22.8 |
| Control Group | Mean Change in Proportion of Days Covered (PDC) by Hydroxyurea | Baseline and 6 months | 13.1 change in percentage of PDC | Standard Deviation 29.7 |
| Control Group | Mean Change in Proportion of Days Covered (PDC) by Hydroxyurea | 6 months and 12 months | -1.9 change in percentage of PDC | Standard Deviation 33.7 |
Comparison: We compared the difference in proportion of days covered by hydroxyurea at two timepoints: (1) from the year prior to study entry to 6 months (the end of the active intervention phase of the trial) and (2) from 6 months to 12 months (the sustainability phase of the trial).p-value: 0.6t-test, 2 sided
Secondary
Mean Change in Parent Youth Concordance Regarding Self-management Responsibility
Concordance between parent and youth scores Sickle Cell Family Responsibility scores for 11 items measuring self-management tasks. Scores range from 0-11 with a higher score indicating better concordance.
Time frame: Baseline, 6 months and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention Group | Mean Change in Parent Youth Concordance Regarding Self-management Responsibility | Baseline to 6 months | 1.6 units on a scale | Standard Deviation 2.4 |
| Intervention Group | Mean Change in Parent Youth Concordance Regarding Self-management Responsibility | 6 months to 12 months | 0.3 units on a scale | Standard Deviation 2.1 |
| Control Group | Mean Change in Parent Youth Concordance Regarding Self-management Responsibility | Baseline to 6 months | 1.4 units on a scale | Standard Deviation 2.5 |
| Control Group | Mean Change in Parent Youth Concordance Regarding Self-management Responsibility | 6 months to 12 months | 0.5 units on a scale | Standard Deviation 2.3 |
Comparison: We hypothesized that, compared to the control group, responsibility for self-management concordance for youth-caregiver dyads in the intervention group would improve from baseline to 6 months.p-value: 0.002Regression, Linear
Comparison: We hypothesized that the improvement in concordance between youth and caregivers for self-management responsibility experienced by the intervention group would be sustained from month 6 to month 12.p-value: 0.23Regression, Linear
Secondary
Mean Change in Youth Score on PedsQL Sickle Cell Disease Module (Disease Specific Quality of Life)
Used to measure sickle cell disease specific health-related quality of life. Scores range from 0-100 with a higher score indicating a better quality of life.
Time frame: Baseline, 9 months and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention Group | Mean Change in Youth Score on PedsQL Sickle Cell Disease Module (Disease Specific Quality of Life) | Baseline to 9 months | 16.4 score on a scale | Standard Deviation 23.3 |
| Intervention Group | Mean Change in Youth Score on PedsQL Sickle Cell Disease Module (Disease Specific Quality of Life) | 9 months to 12 months | -4.3 score on a scale | Standard Deviation 21.9 |
| Control Group | Mean Change in Youth Score on PedsQL Sickle Cell Disease Module (Disease Specific Quality of Life) | Baseline to 9 months | 9.0 score on a scale | Standard Deviation 12 |
| Control Group | Mean Change in Youth Score on PedsQL Sickle Cell Disease Module (Disease Specific Quality of Life) | 9 months to 12 months | -0.7 score on a scale | Standard Deviation 15.7 |
Comparison: We hypothesized that, compared to the control group, sickle cell disease specific quality of life (SC-QOL) for youth in the intervention group would improve from baseline to 9 months.p-value: 0.47Regression, Linear
Comparison: We hypothesized that the improvement in sickle cell disease specific quality of life (SC-QOL) experienced by the intervention group would be sustained from month 9 to month 12.p-value: 0.045Regression, Linear
Secondary
Mean Change in Youth Score on Peds Quality of Life (Generic Quality of Life)
Used to measure health-related quality of life. Scores range from 0-100 with a higher score indicating a better quality of life.
Time frame: Baseline, 4 months, 9 months and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention Group | Mean Change in Youth Score on Peds Quality of Life (Generic Quality of Life) | Baseline to 9 months | 10.3 score on a scale | Standard Deviation 12.6 |
| Intervention Group | Mean Change in Youth Score on Peds Quality of Life (Generic Quality of Life) | 9 months to 12 months | -2.5 score on a scale | Standard Deviation 11.6 |
| Control Group | Mean Change in Youth Score on Peds Quality of Life (Generic Quality of Life) | Baseline to 9 months | 2.0 score on a scale | Standard Deviation 12.3 |
| Control Group | Mean Change in Youth Score on Peds Quality of Life (Generic Quality of Life) | 9 months to 12 months | 1.1 score on a scale | Standard Deviation 16.2 |
Comparison: We hypothesized that, compared to the control group, generic quality of life (QOL) for youth in the intervention group would improve from baseline to 9 months.p-value: <0.001Regression, Linear
Comparison: We hypothesized that the improvement in quality of life experienced by the intervention group would be sustained from month 9 to month 12.p-value: 0.04Regression, Linear