Genetic Testing to Understand and Address Renal Disease Disparities Across the United States Pharmacogenetic Substudy (GUARDD-US PGx)

Duke University

Status: Completed

Conditions: Chronic Kidney Disease; Hypertension

Treatments: Other: Timing of return of results

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06748040

Pro00102997_A

U01HG010245 (U.S. NIH Grant/Contract)

U01HG007269 (U.S. NIH Grant/Contract)

U01HG010248 (U.S. NIH Grant/Contract)

U01HG010225 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 1,874 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,874 participants in 2 patient groups

Immediate Return of Results

Active Comparator group

Description:

Immediate return of pharmacogenetic (PGx) results to substudy (APOL1 negative) participant.

Treatment:

Other: Timing of return of results

Delayed Return of Results

Active Comparator group

Description:

Delayed return of pharmacogenetic (PGx) results to substudy (APOL1 negative) participant until after the completion of the 6 month final study visit.

Treatment:

Other: Timing of return of results