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.

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Publisher: Elsevier B.V.
Document Type: Report
Length: 635 words

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Keywords Pharmacogenomics; Blood pressure; Genotype; Chronic kidney disease 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 Author Affiliation: (a) Indiana University School of Medicine, Indianapolis, IN 46202, USA (b) Vanderbilt University Medical Center, Nashville, TN 37232, USA (c) Duke University School of Medicine, Durham, NC 27720, USA (d) Institute for Health Equity Research, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA (e) Duke Clinical Research Institute, Durham, NC 27720, USA (f) Institute for Family Health, New York, NY 10029, USA (g) Meharry Medical College, Nashville, TN 37208, USA (h) McKenzie-Elliott School of Nursing, University of North Carolina at Pembroke, Pembroke, NC 28372, USA (i) Office of Research, University Medical Center New Orleans, New Orleans, LA 70112, USA (j) Baylor Scott & White Health, Baylor University, Robbins Institute for Health Policy & Leadership, Dallas, TX 75246, USA (k) University of Florida College of Medicine -- Jacksonville, Jacksonville, FL 32209, USA (l) University of Florida, College of Pharmacy, Gainesville, FL 32610, USA (m) University of Florida, College of Medicine, Gainesville, FL 32610, USA (n) Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA (o) Bethel Gospel Assembly, New York, NY 10035, USA (p) Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA (q) Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, MD 20892, USA * Correspondence to: C. R. Horowitz, Internal Medicine Associates, 7th Floor 17 East 102nd Street, New York, NY 10029, USA. Article History: Received 16 February 2022; Revised 25 May 2022; Accepted 30 May 2022 (footnote)1 Co-first authors who contributed equally. Byline: Michael T. Eadon (a,1), Kerri L. Cavanaugh (b,1), Lori A. Orlando (c,1), David Christian (d,1), Hrishikesh Chakraborty (c,e), Kady-Ann Steen-Burrell (e), Peter Merrill (e), Janet Seo (d), Diane Hauser (d,f), Rajbir Singh (g), Cherry Maynor Beasley (h), Jyotsna Fuloria (i), Heather Kitzman (j), Alexander S. Parker (k), Michelle Ramos (d), Henry H. Ong (b), Erica N. Elwood (l), Sheryl E. Lynch (a), Sabrina Clermont (d), Emily J. Cicali (l), Petr Starostik (m), Victoria M. Pratt (a), Khoa A. Nguyen (l), Marc B. Rosenman (n), Neil S. Calman (d,f), Mimsie Robinson (o), Girish N. Nadkarni (p), Ebony B. Madden (q), Natalie Kucher (q), Simona Volpi (q), Paul R. Dexter (a), Todd C. Skaar (a), Julie A. Johnson (l), Rhonda M. Cooper-DeHoff [] (l,**), Carol R. Horowitz [] (d,p,*)

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Gale Document Number: GALE|A714831765