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

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.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Response; Weakness, Muscle
• Intervention / Treatment: Drug: NaCl 0.9%; Drug: Methylprednisolone

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 Type: Interventional
• Enrollment (Estimated): 672
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: STEVEN THIESSEN; Phone Number: 003289325294; Email: steven.thiessen@zol.be

Study Locations

• Belgium
  • Genk, Belgium
    • Recruiting
    • Ziekenhuis Oost-Limburg
    • Contact: Steven Thiessen; Phone Number: 89325294; Email: steven.thiessen@zol.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 and mitral valve replacement
  • laparoscopic hemicolectomies
  • thoracoscopic lung resections
  • femoral popliteal and tibial bypass surgery and femoral profundoplasty
  • 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post operative muscle weakness	decrease in muscle strength post-operatively, assessed by comparing the handgrip strength of the dominant hand, measured by the JAMAR dynamometer, on day 1 following surgery as compared to the preoperative value	Pre-operative and Post operative day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post operative muscle weakness	Decrease in muscle strength post-operatively, assessed by comparing the handgrip strength of the dominant hand, measured by the JAMAR dynamometer, on day 3 and 5 following surgery as compared to the preoperative value, if still in the hospital.	Pre-operative and Post operative day 1, 3 and 5
Maximum inspiratory pressure as measure of respiratory muscle function	Maximum inspiratory pressure on day 1, 3 and 5, as compared to pre-operative value, if still in the hospital.	Pre-operative and Post operative day 1, 3 and 5
Post operative fatigue	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	Pre-operative and Post operative day 1, 3, 5 and 28
Quality of recovery (QOR)	Assessed by the QOR-15 scale, scores min 0 - max 150, higher score means worse outcome, assessed on day 1, 3 and 5 as compared to preoperatively	Post operative day 1, 3 and 5
Functioning at 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	Pre-operative and Post operative day 28
Coagulation disorder	biochemical markers of coagulation postoperatively as compared to preoperatively	postoperatively first 24 hours
Sleeping pattern	Assessed by the Consensus Sleep Diary (CSD) in a subset of study population	10 consecutive nights, starting 3 days before surgery
Sleep quality	Assessed by the Pittsburgh Sleep Quality Index (PSQI) in a subet of study population, score range between 0 and 21, higher scores indicate worse sleep quality	3 days before and 10 days after surgery
Sleep chronotype	Assessed by the Munich Chronotype Questionnaire (MCTQ) is a subset of study population	3 days before surgery
Sleeping EEG pattern	Assessed by EEG recording in a subset of study population	first postoperative night

Collaborators and Investigators

• Sponsor: Ziekenhuis Oost-Limburg

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2022
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 31, 2022
• First Submitted That Met QC Criteria: January 31, 2022
• First Posted (Actual): February 2, 2022

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Weakness; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: Z-2021070

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
• product manufactured in and exported from the U.S.: No