@article{b43022492bcb4e318572680d403b5fb1,
title = "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",
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.gov",
keywords = "Blood pressure, Chronic kidney disease, Genotype, Pharmacogenomics",
author = "{For the GUARDD-US Investigators} and Eadon, {Michael T.} and Cavanaugh, {Kerri L.} and Orlando, {Lori A.} and David Christian and Hrishikesh Chakraborty and Steen-Burrell, {Kady Ann} and Peter Merrill and Janet Seo and Diane Hauser and Rajbir Singh and Beasley, {Cherry Maynor} and Jyotsna Fuloria and Heather Kitzman and Parker, {Alexander S.} and Michelle Ramos and Ong, {Henry H.} and Elwood, {Erica N.} and Lynch, {Sheryl E.} and Sabrina Clermont and Cicali, {Emily J.} and Petr Starostik and Pratt, {Victoria M.} and Nguyen, {Khoa A.} and Rosenman, {Marc B.} and Calman, {Neil S.} and Mimsie Robinson and Nadkarni, {Girish N.} and Madden, {Ebony B.} and Natalie Kucher and Simona Volpi and Dexter, {Paul R.} and Skaar, {Todd C.} and Johnson, {Julie A.} and Cooper-DeHoff, {Rhonda M.} and Horowitz, {Carol R.}",
note = "Funding Information: Research reported in this publication was supported by grants from the National Institutes of Health ( U01 HG007269 , U01 HG010232 , U01 HG010248 , U01 HG010231 , U01 HG010245 , U01 HG010225 , and by the NIH IGNITE Network ( https://gmkb.org/ignite/ ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors would also like to thank the GUARDD-US team of academic, community, clinical partners, study coordinators, and staff at study sites, and their partners in the IGNITE Network, a consortium of genomic medicine pilot demonstration projects funded and guided by the NHGRI, for their valuable contributions to this project. We would also like to thank the IGNITE Patient, Provider, and Payer Advisory Board and stakeholders at the individual sites, for their devoted time and effort. Funding Information: Research reported in this publication was supported by grants from the National Institutes of Health (U01 HG007269, U01 HG010232, U01 HG010248, U01 HG010231, U01 HG010245, U01 HG010225, and by the NIH IGNITE Network (https://gmkb.org/ignite/). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors would also like to thank the GUARDD-US team of academic, community, clinical partners, study coordinators, and staff at study sites, and their partners in the IGNITE Network, a consortium of genomic medicine pilot demonstration projects funded and guided by the NHGRI, for their valuable contributions to this project. We would also like to thank the IGNITE Patient, Provider, and Payer Advisory Board and stakeholders at the individual sites, for their devoted time and effort. Publisher Copyright: {\textcopyright} 2022",
year = "2022",
month = aug,
doi = "10.1016/j.cct.2022.106813",
language = "English (US)",
volume = "119",
journal = "Contemporary Clinical Trials",
issn = "1551-7144",
publisher = "Elsevier Inc.",
}
