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Multicenter Study
. 2022 Aug:119:106813.
doi: 10.1016/j.cct.2022.106813. Epub 2022 Jun 1.

Design and rationale of GUARDD-US: A pragmatic, randomized trial of genetic testing for APOL1 and pharmacogenomic predictors of antihypertensive efficacy in patients with hypertension

Michael T Eadon  1 , Kerri L Cavanaugh  2 , Lori A Orlando  3 , David Christian  4 , Hrishikesh Chakraborty  5 , Kady-Ann Steen-Burrell  6 , Peter Merrill  6 , Janet Seo  4 , Diane Hauser  7 , Rajbir Singh  8 , Cherry Maynor Beasley  9 , Jyotsna Fuloria  10 , Heather Kitzman  11 , Alexander S Parker  12 , Michelle Ramos  4 , Henry H Ong  2 , Erica N Elwood  13 , Sheryl E Lynch  1 , Sabrina Clermont  4 , Emily J Cicali  13 , Petr Starostik  14 , Victoria M Pratt  1 , Khoa A Nguyen  13 , Marc B Rosenman  15 , Neil S Calman  7 , Mimsie Robinson  16 , Girish N Nadkarni  17 , Ebony B Madden  18 , Natalie Kucher  18 , Simona Volpi  18 , Paul R Dexter  1 , Todd C Skaar  1 , Julie A Johnson  13 , Rhonda M Cooper-DeHoff  19 , Carol R Horowitz  20 ; GUARDD-US Investigators
Affiliations
Multicenter Study

Design and rationale of GUARDD-US: A pragmatic, randomized trial of genetic testing for APOL1 and pharmacogenomic predictors of antihypertensive efficacy in patients with hypertension

Michael T Eadon et al. Contemp Clin Trials. 2022 Aug.

Abstract

Rationale and objective: APOL1 risk alleles are associated with increased cardiovascular and chronic kidney disease (CKD) risk. It is unknown whether knowledge of APOL1 risk status motivates patients and providers to attain recommended blood pressure (BP) targets to reduce cardiovascular disease.

Study design: Multicenter, pragmatic, randomized controlled clinical trial.

Setting and participants: 6650 individuals with African ancestry and hypertension from 13 health systems.

Intervention: APOL1 genotyping with clinical decision support (CDS) results are returned to participants and providers immediately (intervention) or at 6 months (control). A subset of participants are re-randomized to pharmacogenomic testing for relevant antihypertensive medications (pharmacogenomic sub-study). CDS alerts encourage appropriate CKD screening and antihypertensive agent use.

Outcomes: Blood pressure and surveys are assessed at baseline, 3 and 6 months. The primary outcome is change in systolic BP from enrollment to 3 months in individuals with two APOL1 risk alleles. Secondary outcomes include new diagnoses of CKD, systolic blood pressure at 6 months, diastolic BP, and survey results. The pharmacogenomic sub-study will evaluate the relationship of pharmacogenomic genotype and change in systolic BP between baseline and 3 months.

Results: To date, the trial has enrolled 3423 participants.

Conclusions: The effect of patient and provider knowledge of APOL1 genotype on systolic blood pressure has not been well-studied. GUARDD-US addresses whether blood pressure improves when patients and providers have this information. GUARDD-US provides a CDS framework for primary care and specialty clinics to incorporate APOL1 genetic risk and pharmacogenomic prescribing in the electronic health record.

Trial registration: ClinicalTrials.govNCT04191824.

Keywords: Blood pressure; Chronic kidney disease; Genotype; Pharmacogenomics.

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Conflict of interest statement

Declaration of competing interest:

The authors have nothing to disclose.

Figures

Figure 1:
Figure 1:
GUARDD-US study design. After obtaining written consent, eligible subjects are randomized 1:1 in the control or intervention arms. In the control arm, subjects receive delayed genetic testing with return of results after completion of the study at 6 months. In the intervention arm, subjects and their providers receive immediate disclosure of their APOL1 test results. The primary outcome is change in systolic blood pressure at 3 months between the control and intervention subjects with a high-risk APOL1 genotype. Subjects with a low-risk APOL1 genotype are not included in the primary outcome measure. A subset of the APOL1-LR subjects are re-randomized to test the efficacy of immediate and delayed antihypertensive pharmacogenomic testing. All subjects receive their APOL1 and pharmacogenomic test results at the conclusion of the study.
Figure 2:
Figure 2:
Recruitment from 13 health systems is distributed across 10 geographic regions in the United States.
See this image and copyright information in PMC

References

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