CORTERAS STUDY: The Effect of Corticosteroids on Early Recovery After Major Surgery in Elderly Patients

Sponsor

Ziekenhuis Oost-Limburg (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05220319

Collaborator

(none)

672

Enrollment

Arms

24.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Major surgery induces a systemic inflammatory response, which can influence the post-operative morbidity, such as coagulation disorders and post-operative muscle weakness, hampering early recovery after surgery.

Single administration of high dose corticosteroids is known to reduce this inflammatory response and could possibly improve the post-operative outcome.

The CORTERAS study will evaluate the effect of administration of corticosteroids, as compared to no corticosteroids, on postoperative muscle weakness and quality of recovery after surgery in elderly patients.

Condition or Disease	Intervention/Treatment	Phase
Inflammatory Response Weakness, Muscle	Drug: Methylprednisolone Drug: NaCl 0.9%	Phase 4

Detailed Description

The number of elderly patients undergoing surgery is expected to increase in the coming years, due to the increase in life expectancy in the developing world. Compared to younger surgical patients, the older patients are at greater risk of mortality and morbidity after surgery.

Post-operative fatigue is an important complication after surgery. Not only is it reported by patients as one of the most distressing symptoms, it is also thought to be a significant contributor to delayed recovery after surgery. From a pathophysiological point of view, muscle weakness could be a major contributor to this post-operative fatigue.

Recent studies showed a profound reduction in muscle strength after surgery in elderly patients, which lasted for more than 3 months after surgery. This decrease in muscle strength might be induced by an excessive inflammatory response to surgery.

Glucocorticosteroids are capable of tampering an excessive inflammatory response to surgery and could improve the quality of recovery after surgery. However, a possible effect on post-operative muscle weakness hasn't been specifically investigated.

Therefore, the main objective of this prospective clinical trial is to evaluate the effect of corticosteroids on early post-operative outcome, focusing on muscle weakness, in elderly patients (≥60 years) undergoing surgery.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

672 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

CORTERAS STUDY: The Effect of Corticosteroids on Early Recovery After Major Surgery in Elderly Patients

Anticipated Study Start Date :

Feb 1, 2022

Anticipated Primary Completion Date :

Feb 1, 2024

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 100 ml of NaCl 0,9%, not containing corticosteroids, given at induction of anaesthesia, before surgery. If a patient will receive cardiopulmonary bypass (CPB) during his operation, a repeat dose of 100 ml of NaCl 0,9% will be administered at the beginning of CPB.	Drug: NaCl 0.9% 100 ml NaCl0,9% as an IV injection at the induction of anaesthesia but before surgery. If CPB is required an additional 100ml will be given.
Active Comparator: Methylprednisolone 250 mg of methylprednisolone made up with 100 ml NaCl 0,9%, given at the induction of anaesthesia, before surgery. If a patient will receive cardiopulmonary bypass (CPB) during his operation, a repeat dose of 250 mg methylprednisolone will be administered at the beginning of CPB.	Drug: Methylprednisolone 250 mg Methylprednisolone made up with 100 ml NaCl0,9% as an IV injection at the induction of anaesthesia but before surgery. If CPB is required an additional dose in 100 ml will be given.

Arm

Intervention/Treatment

Placebo Comparator: Placebo

100 ml of NaCl 0,9%, not containing corticosteroids, given at induction of anaesthesia, before surgery. If a patient will receive cardiopulmonary bypass (CPB) during his operation, a repeat dose of 100 ml of NaCl 0,9% will be administered at the beginning of CPB.

Drug: NaCl 0.9%

100 ml NaCl0,9% as an IV injection at the induction of anaesthesia but before surgery. If CPB is required an additional 100ml will be given.

Active Comparator: Methylprednisolone

250 mg of methylprednisolone made up with 100 ml NaCl 0,9%, given at the induction of anaesthesia, before surgery. If a patient will receive cardiopulmonary bypass (CPB) during his operation, a repeat dose of 250 mg methylprednisolone will be administered at the beginning of CPB.

Drug: Methylprednisolone

250 mg Methylprednisolone made up with 100 ml NaCl0,9% as an IV injection at the induction of anaesthesia but before surgery. If CPB is required an additional dose in 100 ml will be given.

Outcome Measures

Primary Outcome Measures

Post operative muscle weakness [Pre-operative and Post operative day 1]
decrease in muscle strength post-operatively, assessed by comparing the handgrip strength of the dominant hand, measured by the CAMRY dynamometer, on day 1 following surgery as compared to the preoperative value

Secondary Outcome Measures

Post operative muscle weakness [Pre-operative and Post operative day 1, 3 and 5]
Decrease in muscle strength post-operatively, assessed by comparing the handgrip strength of the dominant hand, measured by the CAMRY dynamometer, on day 3 and 5 following surgery as compared to the preoperative value, if still in the hospital.
Maximum inspiratory pressure as measure of respiratory muscle function [Pre-operative and Post operative day 1, 3 and 5]
Maximum inspiratory pressure on day 1, 3 and 5, as compared to pre-operative value, if still in the hospital.
Post operative fatigue [Pre-operative and Post operative day 1, 3, 5 and 28]
Assessed by the Chalder fatigue Questionnaire - 11 items, scores min 0 - max 33, higher score means worse outcome: post-operative day 1, 3, 5 and 28, as compared to preoperatively
Quality of recovery (QOR) [Post operative day 1, 3 and 5]
Assessed by the QOR-15 scale, scores min 0 - max 150, higher score means worse outcome, assessed on day 1, 3 and 5
Functioning at day 28 [Pre-operative and Post operative day 28]
EuroQol five dimensions of health (EQ5D), score of 1-5 on each health dimension, higher score means worse outcome + visual analogue scale from 0-100 questionning todays health, lower score means worse outcome. EQ5D is assessed on day 28, as compared to pre-operatively values
Coagulation disorder [postoperatively first 24 hours]
biochemical markers of coagulation postoperatively as compared to preoperatively

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged 60 years or older.
Scheduled for one of the predefined surgical procedures:
off-pump coronary bypass surgery
on-pump coronary bypass surgery
aortic valve replacement
laparoscopic hemicolectomies
thoracoscopic lung resections
femoral popliteal and tibial bypass surgery
laparoscopic radical prostatectomies

Exclusion Criteria:

Lack of informed consent or inability to give informed consent.
Severe postoperative nausea & vomiting (PONV), needing corticosteroids as PONV prophylaxis.
Urgent, not elective surgery
Hypersensitivity or known allergic reactions to methylprednisolone
Preoperative systemic use of steroids:
Including, but not limited to, the use of corticosteroids > 4 weeks before surgery of at least 4 mg methylprednisolone equivalents.
Excluding inhalational and topical steroids
Preexisting muscle disease o Including, but not limited to: Steinert's disease, amyotrophic lateral sclerosis (ALS), Duchenne dystrophy, amputation of dominant arm or hand.