Chronic Kidney Disease, Hypertension
Conditions
Keywords
Kidney Disease, Genetic testing, Pharmacogenomics, Hypertensive medications
Brief summary
This is a substudy of GUARDD-US (Genetic testing to Understand and Address Renal Disease Disparities across the United States, NCT04191824). Its primary purpose is to determine the effect of knowledge of genetic test results that predict efficacy of various antihypertensive medications on change in SBP (systolic blood pressure) from baseline to 3 months in APOL1 (apolipoprotein L1) negative individuals at participating sites.
Detailed description
GUARDD-US includes a substudy that randomizes participants in the Intervention arm who are from the PGx substudy participating sites and who test negative for APOL1 to PGx Intervention (i.e., immediate PGx ROR) and PGx Control (i.e., delayed PGx ROR) in a 1:1 ratio. This substudy will compare outcomes between participants in the PGx Control group and the PGx Intervention group. New data show that genetic differences may cause patients to respond differently antihypertensive medication therapy. Pharmacogenomics may help guide initial or add-on antihypertensive therapy management. However, the impact of PGx testing on BP has not been studied in clinical trials among general or African ancestry populations. Population for PGx Substudy: Participants from Randomized Population who are randomized to Intervention and who test negative for APOL1. Only participants from PGx-substudy participating sites are included in this population. Substudy Analyses: Major primary endpoint analyses conducted for the APOL1 main study will be repeated for the PGx substudy focusing on differences in outcomes between APOL1 negative individuals with immediate PGx ROR (PGx Intervention) and APOL1 negative individuals with delayed PGx ROR (PGx Control).
Interventions
Participants will be randomized to immediate versus delayed return of PGx results.
Sponsors
National Human Genome Research Institute (NHGRI)
Icahn School of Medicine at Mount Sinai
University of Florida
Indiana University School of Medicine
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Immediate versus delayed return of pharmacogenetics (PGx) testing results to provider and participant.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Self reported African ancestry * English Speaking * Age 18-70 years * Have diagnosis of hypertension: Diagnosis of hypertension is defined by either: * ICD10 diagnosis codes (i.e., I10; I11.x; I12.x; I13.x; I16.x) OR * On active antihypertensive therapy for indication of hypertension OR * Having systolic blood pressure of 140 mm Hg or greater in at least 2 of the last 3 consecutive recorded values in the EHR OR * Having hypertension in the patient's medical record problem list * Have been seen at ≥1 time in past year at a participating primary care site * Either: 1) do not have diabetes and do not have CKD, or 2) have CKD; Participants with diabetes may be included as long as they also have CKD. CKD is defined by either: A) ICD10 codes (i.e., N18.x; E08.22; E09.22; E10.22; E11.22;E13.22 (exclude Z94.0; N18.6; Z99.2)) OR B) Microalbumin/proteinuria level \>30 mg/g for 2 time periods ≥ 3 months. Values taken within 12 months of enrollment, unless 2 values are unavailable, then review within 24 months of enrollment. OR C) 15 ≤ eGFR ≤ 60 ml/min for 2 time periods ≥ 3 months. GFRs are taken within 12 months of enrollment, unless 2 values are unavailable, then review within 24 months. Diabetes is defined by: HbA1c ≥ 6.5 at least one time in the last year OR ICD10 diagnosis codes OR Having diabetes in the patient's medical record problem list.
Exclusion criteria
* Have diabetes, but no CKD. * Are currently on dialysis (ICD 10 codes N18.6, Z99.2 and Z94.0) * Have ESRD (eGFR\<15 ml/min) * Have a left ventricular assist device (LVAD) * Have a terminal illness * Have patient-reported known pregnancy at time of enrollment * Have had a liver, kidney, or allogeneic bone marrow transplant * Too cognitively impaired to provide informed consent and/or complete the study protocol * Institutionalized or too ill to participate (i.e. incarcerated, psychiatric or nursing home facility) * Plan to move out of the area within 6 months of enrollment * Not a current patient seeing a provider who cares for their hypertension (i.e., family medicine, internal medicine, nephrology, HIV provider, cardiology, hypertension specialists) at a participating site * Previously participated in the GUARDD pilot study OR have previously undergone APOL1 testing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Systolic Blood Pressure From Baseline to 3 Months for APOL1 Negative Participants | Baseline to 3 month study visit |
Countries
United States
Participant flow
Recruitment details
Participants were recruited by providers who care for participants with hypertension (including, for example, general internists, primary care providers, and nephrologists).
Pre-assignment details
Among the 6754 participants randomized into the GUARDD-US main trial, 1874 participants were further randomized into the GUARDD-US PGx substudy. These participants were assigned to the 'Immediate Return of Results' treatment group in the main trial, were from PGx-substudy participating sites and had an APOL1 negative phenotype. For this study, APOL1 negative refers to participants without 2 high risk alleles at the APOL1 locus also termed as without APOL1-HR.
Participants by arm
| Arm | Count |
|---|---|
| Immediate Return of Results Immediate return of pharmacogenetic (PGx) results to substudy (APOL1 negative/without APOL1-HR) participant. | 953 |
| Delayed Return of Results Delayed return of pharmacogenetic (PGx) results to substudy (APOL1 negative/without APOL1-HR) participant until after the completion of the 6 month final study visit. | 921 |
| Total | 1,874 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 4 |
| Overall Study | Lost to Follow-up | 134 | 132 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | Immediate Return of Results | Total | Delayed Return of Results |
|---|---|---|---|
| Age, Continuous | 55.3 years STANDARD_DEVIATION 10.4 | 55.0 years STANDARD_DEVIATION 10.7 | 54.7 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 32 Participants | 67 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 917 Participants | 1796 Participants | 879 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 11 Participants | 7 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 852 Participants | 1680 Participants | 828 Participants |
| Race/Ethnicity, Customized Race More than one race | 65 Participants | 125 Participants | 60 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race North African/Mediterranean | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Unknown or Not Reported | 31 Participants | 63 Participants | 32 Participants |
| Race/Ethnicity, Customized Race White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 953 Participants | 1874 Participants | 921 Participants |
| Sex: Female, Male Female | 610 Participants | 1200 Participants | 590 Participants |
| Sex: Female, Male Male | 343 Participants | 674 Participants | 331 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 953 | 4 / 921 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Change in Systolic Blood Pressure From Baseline to 3 Months for APOL1 Negative Participants
Time frame: Baseline to 3 month study visit
Population: Intent To Treat (ITT) population for PGx substudy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immediate Return of Results | Change in Systolic Blood Pressure From Baseline to 3 Months for APOL1 Negative Participants | -3.7 mmHg | Standard Deviation 19 |
| Delayed Return of Results | Change in Systolic Blood Pressure From Baseline to 3 Months for APOL1 Negative Participants | -3.1 mmHg | Standard Deviation 19 |
p-value: 0.485295% CI: [-2.4, 1.2]t-test, 2 sided