MINSS: Myocardial Injury in Noncardiac Surgery in Sweden

Sponsor

Linkoeping University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03436238

Collaborator

Region Östergötland (Other), Medical Research Council of Southeast Sweden (Other)

1,269

Enrollment

Locations

103.6

Anticipated Duration (Months)

181.3

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this multicentre, prospective, observational study is to identify robust biochemical markers that predict adverse cardiovascular outcomes and mortality in patients undergoing major abdominal surgery.

Condition or Disease	Intervention/Treatment	Phase
Perioperative/Postoperative Complications Risk Factor, Cardiovascular

Detailed Description

Inclusion Adults at least 50 years old undergoing elective, major or major/complex abdominal surgery defined according to the Surgical Outcome Risk Tool (www.sortsurgery.com), requiring general anaesthesia and at least one overnight stay. Exclusion Patients with acute coronary syndromes, new or decompensated heart failure at presentation, documented severeaortic stenosis, severely reduced ejection fraction (<40%) and inability to follow the procedures of the study or lack of capacity to give informed consent. Transplantation, trauma, endocrine, vascular and endovascular surgical procedures will also be excluded due to their distinct risk profiles compared with the intended population. Outcome The composite endpoint is all-cause mortality at 30 days and MACCE, the latter defined as nonfatal cardiac arrest, acute MI, congestive heart failure, new cardiac arrhythmia, angina and stroke. Secondary endpoints are 365-day all-cause mortality and MACCE. Data collection Relevant clinical and peri-operative data for example comorbidities, RCRI, ASA-PS score, type and length of surgery, blood loss and intra-operative lowest blood pressure will be collected.

Plasma levels of hsTnT, NTproBNP, Copeptin, MR-proADM and CT-proET1 will be measured at five sampling points: pre-operatively, immediately postoperatively, and on Days 1 to 3 postoperatively or until discharge. Data on MACCE will be obtained from patient records and structured telephone interviews at 30 and 365 days by assessors blinded to the results of the biomarker analyses.

Statistics Based on an assumed incidence of MINS of 10%(1) and 365-day mortality in the non-MINS group of 11% (estimate based on current data from the Swedish Perioperative Registry), the required sample size to detect an effect size of 10% is 1142. To account for drop-outs and missing data, we will recruit up to 1600 patients.

Receiver operating curve analysis will be used to determine the optimal threshold of each biomarker in predicting mortality/MACCE. The net reclassification index will be used to assess if biomarkers confer added value to the RCRI for the classification of MACCE.

A multivariable Cox proportional hazard models will be used to test the independent prognostic value of biomarkers. The sample size allows for adjustment of the following prespecified variables, selected on the basis of clinical plausibility and prior evidence: age, sex, ASA-PS class, RCRI, Charlson Comorbidity Index, length and type of surgery, presence of intra-operative hypotension, pre-operative creatinine and haemoglobin, biomarkers (alone and in combination). An independent statistical analysis will be conducted after recruitment of 600 patients to assess the frequency of outcomes and missing data, after which the sample size may be adjusted.

NOTE: An independent assessment by the Data Safety and Monitoring Board (DSMB) specifically addressing a revision of the sample size found that a total of 1269-1334 participants would be required for the study. This was based on a lower than expected rate of missing data (7.6% at DSMB assessment vs. expected 33% during study planning).

We therefore revised the sample size to 1269 (-1334) participants on 2 September 2019.

UPDATE 26 Feb 2022:

This study (including outcomes up to 30d after surgery) has been published:

https://www.bjanaesthesia.org/article/S0007-0912(21)00649-8/fulltext

Long-term outcome study and prespecified substudies are ongoing.

Study Design

Study Type:

Observational

Actual Enrollment :

1269 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Myocardial Injury in Noncardiac Surgery in Sweden (MINSS) Study: Multi-centre, Observational Cohort Study of Patients Undergoing Elective, Major Abdominal Surgery.

Actual Study Start Date :

May 15, 2017

Actual Primary Completion Date :

Mar 31, 2020

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
MINSS cohort Adult patients >= 50 years old undergoing elective, major, abdominal surgery requiring at least one overnight stay in hospital. Major abdominal surgery is defined as those classified as major OR major/complex by the Surgical Outcome Risk Tool (SORT) (www.sortsurgery.com).

Outcome Measures

Primary Outcome Measures

30-day mortality [30 days post surgery]
All-cause mortality at 30 days post-surgery.
30-day MACCE [30 days post surgery]
Major adverse cardio- cerebrovascular events (MACCE) at 30 days post-surgery.

Secondary Outcome Measures

12-month mortality [12 months post surgery]
All-cause mortality at 12 months post-surgery.
12-month MACCE [12 months post surgery]
Major adverse cardio- cerebrovascular events (MACCE) at 12 months post-surgery.

Other Outcome Measures

Net reclassification index (NRI) [30 days post surgery]
The NRI will be calculated to assess if a preoperative elevated biomarker panel confers added value over RCRI
Long term mortality [3 years and 5 years]
Long-term mortality will be extracted from the Swedish Registry of Deaths

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients undergoing elective, major abdominal surgery*.

(*Major abdominal surgery requiring general anaesthesia, and requiring at least one overnight stay. Major abdominal surgery is defined as those classified as major OR major/complex by the Surgical Outcome Risk Tool (SORT) (www.sortsurgery.com).

In essence major surgery is one that penetrates and exposes a body cavity or produces a substantial impairment of physical or physiologic function or involves extensive dissection or transection. Examples of a major abdominal surgery include, but are not limited to, any procedure involving a laparotomy or laparoscopic procedures of the stomach, duodenum, small and large intestine and rectum. It also includes but is not limited to procedures on the reproductive system (total abdominal hysterectomy, salpingo-oophorectomy) and genitourinary system (nephrectomy, cystectomy).)

Exclusion Criteria:

Patient not fulfilling inclusion study criteria above and/or clinician refusal and/or non-eligible as defined below.

Patients undergoing the following surgical procedures will NOT be eligible:

transplantation
trauma
endocrine
vascular
endovascular

The presence of any one of the following will also lead to exclusion of the patient:

ACS at presentation (clinical assessment or documentation)
New or decompensated congestive heart failure at presentation (clinical assessment or documentation)
Documented severe aortic stenosis (valve area < 1cm2)
Reduced LVEF (<40%); if no LVEF is available, it will be assumed to be >40%
Inability to follow the procedures of the study, e.g. due to language problems, dementia, etc. of the participant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kristianstad KRYH Hospital	Kristianstad	Skåne	Sweden
2	Eskilstuna Hospital	Eskilstuna		Sweden
3	Ryhov County Hospital	Jönköping		Sweden
4	Skane University Hospital Lund	Lund		Sweden
5	Skane University Hospital Malmö	Malmö		Sweden
6	Vrinnevi Hospital	Norrköping		Sweden
7	Department of Anaesthesia and Intensive Care, Linkoeping University Hospital, Region Östergötland	Linköping	Östergötland	Sweden	50185