Precision Treatment With Angiotensin Converting Enzyme Inhibitor

Precision Treatment Based on Genetic Information Associated With Response to Angiotensin Converting Enzyme Inhibitor

Angiotensin converting enzyme inhibitors (ACEI) are the first-line treatment for high blood pressure and congestive heart failure, and have excellent effects in improving the prognosis of cardiovascular diseases. However, ACEI is frequently discontinued due to its adverse reaction. The adverse reaction to ACEI is not uncommon, especially in Asians. Discontinuation of ACEI is known to increase the risk of poor prognosis of cardiovascular diseases.

Biomarkers for predicting adverse reaction to ACEI have not yet been developed. Recently, genes related to adverse reaction to ACEI have been identified. This study is a randomized prospective study, in which the experimental group decides whether to administer the drug based on genetic information, and the control group decides whether to administer the drug without the information. In the experimental group, participants who are predicted to have a high risk of adverse reation to ACEI will receive angiotensin receptor blockers (ARB), and those who are predicted to have a low risk of adverse reaction will receive ACEI. Control group will receive ACEI. The frequency of adverse reaction will be investigated between control and experimental groups. In the genotyping and control groups, at least 45 and 31 will be enrolled, respectively, and after drug administration, a phone follow-up will be conducted at 3 weeks, followed by a visit at the 6th week, and the study will be terminated.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: genotyping and selection of renin-angiotensin system blocker; Drug: Perindopril

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Yonsei University Health System, Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women over 20 years of age and less than 79 years of age
• Hypertension
• No history of ACEI use

Exclusion Criteria:

• Acute coronary syndrome, cerebrovascular accident, symptomatic peripheral artery disease, or coronary revascularization in the past three months
• Decompensated heart failure
• Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg
• Hemoglobin A1c >9.0%
• Thyroid dysfunction
• Serum transaminase >2 times the upper limit of normal levels
• Serum creatinine >2.0 mg/dL
• Cancer
• Pregnant or breast-feeding women, and women of childbearing potential
• Patients who refused to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; This group will perform genetic study for predicting adverse reaction to ACEI. Based on the result of genetic study, participants will receive ACEI or ARB.	Drug: genotyping and selection of renin-angiotensin system blocker; One of perindopril or candesartan was chosen based on genotyping results on two NELL1 variants.; perindopril 4 mg/d after genotyping; candesartan 8 mg/d after genotyping
Active Comparator: Control; Participants will receive ACEI without genetic study.	Drug: Perindopril; perindopril 4 mg/d without genotyping

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of cough	6 weeks after administration of drug
Incidence of moderate/severe cough	6 weeks after administration of drug

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of any adverse events	6 weeks after administration of drug

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Sang-Hak Lee, Division of Cardiology, Severance Hospital, Yonsei University College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2019
• Primary Completion (Actual): August 2, 2021
• Study Completion (Actual): August 2, 2021

Study Registration Dates

• First Submitted: September 7, 2022
• First Submitted That Met QC Criteria: September 7, 2022
• First Posted (Actual): September 10, 2022

Study Record Updates

• Last Update Posted (Estimate): January 11, 2023
• Last Update Submitted That Met QC Criteria: January 8, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Perindopril
• Other Study ID Numbers: 4-2019-0916

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No