NCT04506372

Management of Angiotensin Inhibitors During the Perioperative Period

Angiotensin-converting Enzyme Inhibitors and Angiotensin Receptor Blockers During the Perioperative Period: to Withdraw or to Continue? A Multicenter Randomized Controlled Trial

• Status: Terminated
• Phase: N/A
• Study type: Interventional
• Enrollment: 342 (actual)
• Sponsor: UMC Utrecht · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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

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

• Surgery
• Angiotensin Hypertension
• Perioperative Complication

Interventions

Type	Name	Description
DRUG	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.
DIAGNOSTIC_TEST	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
BEHAVIORAL	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.
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
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

Timeline

• Start date: 2020-09-11
• Primary completion: 2023-02-06
• Completion: 2023-09-01
• First posted: 2020-08-10
• Last updated: 2023-11-29

Locations

7 sites across 2 countries: Canada, Netherlands