Impact of Renin-Angiotensin System Inhibitors Continuation on Outcome After Major Surgery (STOPORNOT)

May 21, 2024 updated by: Assistance Publique - Hôpitaux de Paris

Impact of Renin-Angiotensin System Inhibitors Continuation on Outcome After Major Surgery : a Multicenter, Prospective, Randomized and Controlled Trial

More than 200 million major surgical procedures are performed annually worldwide. Many of these patients have comorbidities including hypertension and/or heart failure. Chronic treatment of hypertension and/or heart failure very often includes a Renin-Angiotensin System (RAS) inhibitor (Angiotensin-Converting Enzyme Inhibitors (ACE-Is) or Angiotensin Receptor Blockers (ARBs). To stop or not to stop these medications before major surgery remain unknown. Data on management of RAS inhibitors before major surgery and anesthesia remain lacking and matter of debate. It is much likely that the strategy regarding management of RAS inhibitors in the peri-operative setting have important impact on peri-operative complications.

The lack of evidence leads to conflicting guidelines with respect to RAS inhibitors management before major surgery. While French guidelines are to stop RAS inhibitors patients with hypertension to avoid profound anesthestic-drugs-induced hypotension, international guidelines differ. The American heart association task force states that continuation of RAS inhibitors perioperatively is reasonable (class IIa recommendation,level of evidence: B). The purpose of this study is to determine the prognostic impact of withholding vs continuing ARBs before major non cardiac surgery.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Multicenter, prospective, randomized, pragmatic, parallel-group clinical trial. The inclusion visit takes place between 4 months and no later than 3 days before the surgery visit.

  • The randomization will be performed by the anesthesiologist Control group : RAS-I discontinuation Experimental group: RAS-I continuation
  • A prescription for the medication strategy (stopping or pursuing the medication) will be handed to the patient during the anesthesiology consultation.

Five follow-up visits are planned

  • Immediately, one hour after the surgery (Day 0)
  • Then four follow-up visits are planned on day 1, 2, 7 (or hospital discharge) and 28 days+15 days (43 days maximum) after surgery will be collected data and parameters for study endpoints.

End of research visit is the 28 days+15 days (43 days maximum) follow-up visit.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2222

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Paris, France, 75010
        • Hospital Lariboisière

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients requiring major non-cardiac surgery (surgery with an expected duration of more than 2 hours from the surgical incision and a post-operative hospital stay of least 3 days) (according to the study RELIEF, DOI : 10.1056/NEJMoa1801601))
  • Age≥18 years
  • Patients chronically treated (>3 months before surgery) with RAS inhibitors
  • Pregnancy test at inclusion visit for women of childbearing potential Women of childbearing potential must agree to use adequate contraception according to Recommendations related to contraception and pregnancy testing in clinical trials, by Clinical Trial Facilitation Group (CTFG)
  • Signed informed consent

Exclusion Criteria:

  • Emergency surgery (surgical treatment needed within 24 hours)
  • Hyperkalemia (> 5.5mmol/L) known at the time of the anesthetic consultation
  • Patients for which death is deemed imminent and inevitable or patients with an underlying disease process with a life expectancy of less than 1 month
  • Patient with severe renal insufficiency, known at the time of the anesthestic consultation (as defined by estimated glomerular filtration rate (creatinine clearance <15 ml/min/1.73m2 or requiring renal replacement therapy)
  • Patient with preoperative shock (defined by the need for vasoactive drugs before surgery)
  • Inability to obtain informed consent either from the patient.
  • Lack of Social Insurance

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: continuation of the RAS-inhibitors
in the continuation of the RAS-inhibitors arm the treatment will be continued until the morning the day of surgery.
Procedure: continuation of the RAS-inhibitors
drug intake
Active Comparator: discontinuation of the RAS-inhibitors
In this arm : discontinuation of the RAS-inhibitors 48 hours before surgery Patients won't receive the drug on the morning of the day of the surgery.
Procedure: discontinuation of the RAS-inhibitors
no drug intake

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
composite outcome composed of all-cause mortality and major postoperative complications within 28 days after surgery.
Time Frame: after surgery until day 28

Complications will be validated by an adjudication committee, blinded to the treatment arm.

Death; Acute Myocardial infarction; Arterial or venous thrombosis; Stroke; Acute pulmonary oedema; Post-operative cardiogenic shock; Acute severe hypertension crisis; Cardiac arrhythmia requiring therapeutic intervention; Postoperative episodes of sepsis; Postoperative respiratory complication; Need for unplanned intensive care unit admission or readmission; Acute kidney injury: KDIGO criteria Baseline serum creatinine is obtained from the pre-operative blood sample; Surgical complications: need for reoperation for any reason and radiologic interventions for abscess drainage; Severe Hyperkalemia: serum potassium level >5.5 mmol/L and requiring therapeutic intervention (insulin/glucose infusion and/or sodium bicarbonate infusion and/or intravenous B2 agonists and/or intravenous calcium gluconate and/or renal replacement therapy and/or ventricular tachycardia or ventricular fibrillation).
after surgery until day 28

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Episodes of hypotension
Time Frame: during anesthesia and surgery
Episodes requiring vasopressors administration
during anesthesia and surgery
Acute kidney injury
Time Frame: after surgery until day 28
according to the KDIGO criteria
after surgery until day 28
Maximum SOFA score
Time Frame: from postoperative day 1 to day 7
patients admitted to ICU
from postoperative day 1 to day 7
Duration of hospital stay
Time Frame: after surgery until day 28
Patients who will be outside the hospital but in other types of health care facilities at day 28 will be considered to have been discharged home
after surgery until day 28
Hospital free-days
Time Frame: censored at 28 days following surgery
Duration after hospital discharge
censored at 28 days following surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Eienne Gayat, MD, PhD, Hospital Laribioisière, APHP

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 6, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 24, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 24, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 11, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 14, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 15, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 22, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 21, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P160933J

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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