Clinical trial NCT04506372: Management of Angiotensin Inhibitors During the Perioperative Period
Official title: Angiotensin-converting Enzyme Inhibitors and Angiotensin Receptor Blockers During the Perioperative Period: to Withdraw or to Continue? A Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Surgery
Angiotensin Hypertension
Perioperative Complication
Keywords: Noncardiac surgery
Angiotensin inhibitors
Perioperative management
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2020-08-10
Enrollment: 342
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled clinical trial
Primary purpose: PREVENTION

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Postoperative acute kidney injury
timeFrame: Within two days after surgery
Secondary outcomes:
measure: Postoperative myocardial injury
timeFrame: Within two days after surgery
measure: Acute postoperative myocardial injury
timeFrame: Within two days after surgery
measure: Intraoperative hypotension
timeFrame: From the start of anesthesia until the end of surgery
measure: Postoperative hypotension
timeFrame: From the end of surgery up to and including the second postoperative day
measure: Preoperative hypertension
timeFrame: Within 24 hours before start of anesthesia
measure: Postoperative hypertension
timeFrame: From the end of surgery up to and including the second postoperative day
measure: Length of stay
timeFrame: Within three months after surgery
measure: Kidney function loss
timeFrame: Within three months after surgery
measure: Acute kidney function loss
timeFrame: Within two days after surgery
measure: End-stage renal disease
timeFrame: Within three months after surgery
measure: Major cardiovascular complications
timeFrame: Within three months after surgery
measure: Mortality
timeFrame: Within three months after surgery
measure: Quality of life
timeFrame: At three months after surgery
measure: Disability
timeFrame: At three months after surgery
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network Toronto
state: Ontorio
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC location AMC
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC location VU
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Nieuwegein
country: Netherlands
facility: Antonius Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: UMC Utrecht
name: Judith van Waes, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UMC Utrecht
name: Wilton van Klei, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: