Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03436238 |
| Other study ID # |
MINSS |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 15, 2017 |
| Est. completion date |
December 31, 2025 |
Study information
| Verified date |
January 2023 |
| Source |
Linkoeping University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
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
UPDATE 11 Jan 2023:
The following preplanned substudies are ongoing:
1. Effect of myocardial injury (MINS) on quality of recovery in patients undergoing major
abdominal procedures in Sweden.
The aim of the study is to investigate the postoperative quality of recovery (QoR) and
the disability-free survival (DFS) among patients undergoing major abdominal surgery
with and without perioperative myocardial injury in non-cardiac surgery (MINS). Our
hypothesis is that patients with MINS have a poorer QoR and reduced DFS at short- and
long-term follow-up.
P:nested, cohort sub study within the Myocardial Injury in Noncardiac Surgery in Sweden
(MINSS, NCT 03436238) study including patients from 2 participating hospitals E: Acute
perioperative myocardial injury, defined as an increase in hsTnT≥14 ng L-1 above
baseline value and measured at days 0-3 postoperatively.
C: No perioperative myocardial injury O:Postoperative Quality of Recovery (QoR-15)
scores at 7-10 days, 30-days and 1-year after surgery compared to the baseline.
Secondary outcome is Disability Free Survival at 30-days and 1-year after surgery. DFS
is defined as alive and WHODAS score of ≤ 25%.
2. The Effect of Perioperative Haemoglobin Decrease on Long-term Surgical Outcomes.
The aim of this study is to investigate the effect of perioperative decrease in
haemoglobin (Hb) level on the long-term outcomes of patients undergoing major abdominal
surgery.
P:We will include all patients enrolled in the MINSS study if there are available
post-operative Hb measurement(s) and 1-year follow-up data.
E:perioperative decrease in Hb level is the exposure variable of this study. C:various
strata of perioperative Hb decrease O:The primary outcome of this study is the composite
of one-year all-cause mortality and major adverse cardiovascular and cerebrovascular
events (MACCE). The secondary outcome is 30-day post-operative complications defined as
MACCE, re-operation, anastomosis leakage, post-operative infections or bleeding, renal
or respiratory failure and pulmonary embolism
3. Incidence and trajectories of subclinical postoperative acute kidney injury (sPO-AKI),
postoperative acute kidney injury (PO-AKI) and postoperative acute kidney disease
(PO-AKD) among patients undergoing elective, major non-cardiac surgery.
The primary aim of this study is to investigate the incidence of subclinical
postoperative acute kidney injury (sPO-AKI), postoperative acute kidney injury (PO-AKI)
and postoperative acute kidney disease (PO-AKD) and the trajectory of sPO-AKI, among
patients undergoing elective, major non-cardiac surgery.
Secondary aims are to evaluate the relationship between sPO-AKI and major adverse kidney
events by 30 days (MAKE30) and all-cause mortality at 30 days postoperatively as well as
chronic kidney disease (CKD) at one year postoperatively.
P: nested, cohort sub study within the Myocardial Injury in Noncardiac Surgery in Sweden
(MINSS, NCT 03436238) study including patients from 2 participating hospitals E:Serum
creatinine (sCr) measured preoperatively and days 0-3 postoperatively, sCr obtained from
patient charts between day 4-365 and occurrence of ICD codes N17.9, N18.X, N19.9 and
N99.9 between day 0-365.
C: no increase in sCr O: The primary outcome is incidence of sPO-AKI, PO-AKI and PO-AKD,
as defined below.
The secondary outcomes are 30-day all-cause mortality, MAKE 30, and CKD at 1-year
post-surgery
4. The predictive role of MR-proADM for postoperative infections after major non-cardiac
surgery: a sub-study of MINSS The primary aim of this study is to assess if mid-regional
pro-adrenomedullin (MR-proADM) adds value to standard biomarkers in predicting
postoperative infection following major non-cardiac surgery.
The secondary aim is to assess the prognostic value of MR-proADM for 30-day and 12-month
all-cause mortality.
P:Predefined, nested sub-study of the Myocardial Injury in Noncardiac Surgery in Sweden
project (MINSS, NCT 03436238) including patients from Linköping University and Norrköping
Hospitals.
E: Increased plasma values of MR-proADM measured preoperatively and days 0-3 postoperatively.
C: No increase in plasma MR-proADM O:10-day postoperative infections Postoperative infections
are defined as the presence of any of the following: superficial wound infections, deep wound
infections, body cavity infections, pneumonias, urinary tract infections, bloodstream
infections and sepsis as outlined in the European Perioperative Clinical Outcome (EPCO) 2014
definitions.
Secondary outcome:
30-day all-cause mortality. 12-month all-cause mortality. 10-day postoperative sepsis.
5) Phenotypes of perioperative myocardial injury and impact on long-term outcomes among
patients undergoing major elective non-cardiac surgery.
The aim of this study is to evaluate how different phenotypes of myocardial injury may impact
the long-term outcomes among patients undergoing major elective non-cardiac surgery. P:
Pre-planned, sub-study within the Myocardial Injury in Noncardiac Surgery in Sweden (MINSS),
a multicenter, prospective cohort study with available long-term follow-up data.
E:Patients are classified to 1) isolated preoperative increases (>99th URL) in hs-cTnT
(likely chronic), 2) perioperative changes (postop-preop >99th URL) with normal preoperative
hs-cTnT, 3) perioperative changes (postop-preop >99th URL) with increased preoperative
hs-cTnT, 4) only postoperative increases (99th URL between 2 postoperative measurements.
C: no pre-, peri- or postoperative hs-cTnT increases O: The primary outcomes are all-cause
mortality and major adverse cardiovascular and cerebrovascular events (MACCE) at longest
follow up. MACCE is the composite of non-fatal cardiac arrest, myocardial infarction, new
onset angina, new onset heart failure, new onset arrythmia (atrial fibrillation, atrial
flutter, or second- or third-degree atrioventricular block), non-fatal cardiac arrest, and
cerebrovascular insult (stroke and transient ischemic attack).
The secondary outcomes are the individual components of the MACCE definition described above,
cardiac death (according to StEP COMPAC), and extracardiac adverse events (sepsis, acute
kidney injury, pulmonary embolism) at longest follow up.
6) Incidence and outcome of perioperative blood transfusion in patients undergoing major
non-cardiac surgery in Sweden. aims to investigate the incidence and outcome of perioperative
blood transfusion in patients undergoing major non-cardiac surgery in Sweden. Proposed
research questions will include:
1. What is the incidence of perioperative transfusion of blood and blood products?
2. What is the relationship between preoperative anaemia and intraoperative transfusion?
3. What is the relationship between preoperative anaemia and post-operative transfusion?
4. What is the relationship between intra- and post-operative transfusions and mortality,
major adverse cardiovascular and cerebrovascular events and postoperative infections?
P:nested cohort in the MINSS study including 3 participating centres E:perioperative
blood transfusion C:no perioperative blood transfusion O:The primary outcome of this
study is the transfusion of any blood product within the first 3 days of surgery. A
co-primary outcome is the composite of all-cause mortality, major adverse cardiovascular
and cerebrovascular events, and post-operative infection at 30 days post-surgery.
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