Management of Angiotensin Inhibitors During the Perioperative Period

NCT ID: NCT04506372

Last Updated: 2023-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

342 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-11

Study Completion Date

2023-09-01

Brief Summary

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This is a multicenter randomized clinical trial to determine the effect of continuation versus withdrawal of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) in the perioperative period on postoperative complications.

Detailed Description

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Rationale:

Angiotensin inhibitors including angiotensin convertying enzyme inhibitors (ACEI), and angiontensin receptors blockers (ARB) are frequently used to treat patients with chronic hypertension. These drugs reduce morbidity and mortality on the long term. However, when patients who use ACEI or ARB undergo surgery, hypotension may occur in the perioperative period, which may can lead to organ hypoperfusion and damage. On the other hand, when ACEI and ARB are temporarily discontinued in the perioperative period, hypertension may occur which also may lead to complications. Therefore, before surgery the anesthesiologist advises the patient to continue or to temporarily withdraw this drug. Importantly, it is currently unclear which strategy is best, and international guidelines are disconcordant on this point. Policy varies between hospitals and even between anesthesiologists: in some hospitals, patients are advised to temporarily withdraw the ACEI/ARB, whilst in other hospitals patients are advised to continue this drug. The latest research on this topic suggests that perioperative continuation of ACEI/ARB may lead to more complications, but definitive evidence is lacking. Therefore it is important to perform a randomized trial to compare the two options: perioperative continuation versus withdrawal of ACEI/ARB.

Objective:

The objective of this trial is to determine the effect of continuation versus withdrawal of ACEI and ARB in the perioperative period on postoperative complications, expressed as acute kidney injury (AKI), myocardial injury, and quality of life (QoL).

Study design:

This is a multicenter randomized clinical trial.

Study population:

Patients who use ACEI/ARB chronically for treatment of hypertension and who are scheduled for an elective intermediate to high risk non-cardiac surgical procedure with an expected postoperative length of hospital stay of at least 2 days, are eligible for inclusion. Patients who use a combination pill of ACEI/ARB with a diuretic are eligible as well. Patients who use a combination pill ACEIwith another drug will be excluded, as well as patients who use other drugs acting on the renin aldosterone angiotensin system.

Intervention:

The intervention is the withdrawal of ACEI/ARB in the perioperative period, i.e. 24 hours before surgery until 24-48 hours after surgery. The ACEI/ARB medication is resumed on the second or third day after surgery, as soon as the clinical condition allows based on judgement by the attending physician.

This intervention will be compared to perioperative continuation of ACEI/ARB.

Main study parameters/endpoints:

The primary outcome for this study is postoperative acute kidney injury, defined according to the Kidney Disease Improving Global Outcomes (KDIGO) guideline.

Secondary outcomes include postoperative myocardial injury, intraoperative and postoperative hypotension and hypertension, length of stay in the hospital or nursing home, kidney function loss and end-stage renal disease within three months after surgery, major cardiovascular complications (myocardial infarction, coronary revascularization, heart failure, arrhythmia, stroke) within three months after surgery, all-cause mortality within three months after surgery and a quality of life (QoL) assessment.

Conditions

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Surgery Angiotensin Hypertension Perioperative Complication

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized controlled clinical trial
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Intervention group

Perioperative withdrawal of ACEI/ARB.

Group Type EXPERIMENTAL

Perioperative withdrawal of angiotensin converting enzyme inhibitors and angiotenin receptor blockers

Intervention Type DRUG

Withdrawal from 24 hours before surgery until 24-48 hours after surgery. The ACEI/ARB medication is resumed on the second or third day after surgery, as soon as the clinical condition allows based on judgement by the attending physician.

Blood draw

Intervention Type DIAGNOSTIC_TEST

Blood will be drawn to measure creatinin and troponin: once before surgery, on the first and second postoperative day, and within 4-8 weeks after surgery

Diary to register drug adherence

Intervention Type BEHAVIORAL

To register medication adherence, patients will be asked to fill out their medication intake (of ACEI/ARB) in a diary from a week before surgery until surgery.

Quality of life questionnaire

Intervention Type BEHAVIORAL

Patients are asked to fill out a quality of life questionnaire (EQ-5D) before surgery and at three months after surgery

WHODAS questionnaire

Intervention Type BEHAVIORAL

Patients are asked to fill out a questionnaire about disabilities (WHO Disability Assessment Schedule 2.0) before surgery and at three months after surgery

Control group

Perioperative continuation of ACEI/ARB.

Group Type ACTIVE_COMPARATOR

Blood draw

Intervention Type DIAGNOSTIC_TEST

Blood will be drawn to measure creatinin and troponin: once before surgery, on the first and second postoperative day, and within 4-8 weeks after surgery

Diary to register drug adherence

Intervention Type BEHAVIORAL

To register medication adherence, patients will be asked to fill out their medication intake (of ACEI/ARB) in a diary from a week before surgery until surgery.

Quality of life questionnaire

Intervention Type BEHAVIORAL

Patients are asked to fill out a quality of life questionnaire (EQ-5D) before surgery and at three months after surgery

WHODAS questionnaire

Intervention Type BEHAVIORAL

Patients are asked to fill out a questionnaire about disabilities (WHO Disability Assessment Schedule 2.0) before surgery and at three months after surgery

Interventions

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Perioperative withdrawal of angiotensin converting enzyme inhibitors and angiotenin receptor blockers

Withdrawal from 24 hours before surgery until 24-48 hours after surgery. The ACEI/ARB medication is resumed on the second or third day after surgery, as soon as the clinical condition allows based on judgement by the attending physician.

Intervention Type DRUG

Blood draw

Blood will be drawn to measure creatinin and troponin: once before surgery, on the first and second postoperative day, and within 4-8 weeks after surgery

Intervention Type DIAGNOSTIC_TEST

Diary to register drug adherence

To register medication adherence, patients will be asked to fill out their medication intake (of ACEI/ARB) in a diary from a week before surgery until surgery.

Intervention Type BEHAVIORAL

Quality of life questionnaire

Patients are asked to fill out a quality of life questionnaire (EQ-5D) before surgery and at three months after surgery

Intervention Type BEHAVIORAL

WHODAS questionnaire

Patients are asked to fill out a questionnaire about disabilities (WHO Disability Assessment Schedule 2.0) before surgery and at three months after surgery

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

* Chronic ACEI or ARB use for the treatment of hypertension. Patients who use a com-bination pill with a diuretic are eligible as well;
* Scheduled for elective intermediate to high risk noncardiac surgery, defined according to the European Society of Cardiology / European Society of Anesthesiology guidelines on noncardiac surgery;
* Expected postoperative length of stay of at least two days.

Exclusion Criteria

* Severe chronic kidney disease, defined as GFR\<30 ml/min/1.73 m2;
* ACEI/ARB use for the treatment of chronic systolic heart failure, defined as left ven-tricular ejection fraction ≤40%;
* ACEI/ARB use within one year after ST-elevated myocardial infarction, according to the fourth universal definition of myocardial infarction;
* Transplant surgery;
* ACEI/ARB use in a combination pill together with a drug other than a diuretic, including calcium channel blockers, beta-blockers and neprilysin inhibitors;
* Use of drugs acting on the renin-angiotensin-aldosterone system other than ACEI/ARB, e.g. aliskiren.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role collaborator

UMC Utrecht

OTHER

Sponsor Role lead

Responsible Party

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Judith van Waes

J.A.R. van Waes, MD PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Judith van Waes, MD PhD

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Wilton van Klei, MD PhD

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Locations

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University Health Network Toronto

Toronto, Ontorio, Canada

Site Status

Amsterdam UMC location AMC

Amsterdam, , Netherlands

Site Status

Amsterdam UMC location VU

Amsterdam, , Netherlands

Site Status

Amphia Hospital

Breda, , Netherlands

Site Status

Antonius Hospital

Nieuwegein, , Netherlands

Site Status

Erasmus MC

Rotterdam, , Netherlands

Site Status

UMC Utrecht

Utrecht, , Netherlands

Site Status

Countries

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Canada Netherlands

Related Links

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Other Identifiers

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AIPOP

Identifier Type: -

Identifier Source: org_study_id