Management of Angiotensin Inhibitors During the Perioperative Period

Surgery Clinical Trial

— AIPOP  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04506372
• Other study ID #: AIPOP
• Status: Terminated
• Phase: N/A
• Start date: September 11, 2020
• Est. completion date: September 1, 2023

Study information

• Verified date: November 2023
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 342
• Est. completion date: September 1, 2023
• Est. primary completion date: February 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Angiotensin Hypertension
• Hypertension
• Perioperative Complication
• Surgery

Intervention

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.
• 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
• 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

Locations

Country	Name	City	State
Canada	University Health Network Toronto	Toronto	Ontorio
Netherlands	Amsterdam UMC location AMC	Amsterdam
Netherlands	Amsterdam UMC location VU	Amsterdam
Netherlands	Amphia Hospital	Breda
Netherlands	Antonius Hospital	Nieuwegein
Netherlands	Erasmus MC	Rotterdam
Netherlands	UMC Utrecht	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
UMC Utrecht	ZonMw: The Netherlands Organisation for Health Research and Development

Countries where clinical trial is conducted

Canada,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Postoperative acute kidney injury	Postoperative acute kidney injury, defined according to the Kidney Disease Improving Global Outcomes (KDIGO) guideline.	Within two days after surgery
Secondary	Postoperative myocardial injury	Postoperative myocardial injury, defined as an increased level of serum troponin above the clinical cut-off value	Within two days after surgery
Secondary	Acute postoperative myocardial injury	Acute postoperative myocardial injury, defined as an absolute postoperative increase in serum troponin of more than clinical cut-off value as compared to the preoperative value	Within two days after surgery
Secondary	Intraoperative hypotension	Intraoperative hypotension, defined as a mean arterial pressure <65 mmHg for at least 10 minutes	From the start of anesthesia until the end of surgery
Secondary	Postoperative hypotension	Postoperative hypotension, defined as a mean arterial pressure <65 mmHg	From the end of surgery up to and including the second postoperative day
Secondary	Preoperative hypertension	Preoperative severe hypertension, defined as blood pressure >180/110 mmHg	Within 24 hours before start of anesthesia
Secondary	Postoperative hypertension	Postoperative severe hypertension, defined as blood pressure >180/110 mmHg	From the end of surgery up to and including the second postoperative day
Secondary	Length of stay	Length of stay in hospital or nursing home	Within three months after surgery
Secondary	Kidney function loss	Decline in glomerular filtration rate as compared to before surgery	Within three months after surgery
Secondary	Acute kidney function loss	Decline in glomerular filtration rate as compared to before surgery	Within two days after surgery
Secondary	End-stage renal disease	End-stage renal disease, defined as renal disease requiring dialysis or organ transplantation	Within three months after surgery
Secondary	Major cardiovascular complications	Major cardiovascular complications (myocardial infarction, coronary revascularization, heart failure, arrhythmia, stroke)	Within three months after surgery
Secondary	Mortality	All-cause mortality	Within three months after surgery
Secondary	Quality of life	Quality of life based on the EuroQoL 5D questionnaire	At three months after surgery
Secondary	Disability	Disability at three months after surgery based on the World Health Organization Disability Activity Score (WHODAS): Change in WHODAS as compared to before surgery (continuous measure); Clinically important change in WHODAS defined as an increase of 5% or more as compared to before surgery; Disability free survival defined as WHODAS <16%; Clinically important disability defined as WHODAS >35%.	At three months after surgery

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