Dexamethasone, olanzapine, hemodynamics, and ventilation in cardiac surgery (GLORIOUSII)

Phase 3

Recruiting

• Conditions: We investigate the efficacy of two pharmaceutical interventions for reducing mortality and organ damage, and shortening length of hospital stay in patients undergoing heart surgery (i.e. coronary artery bypass grafting and/or heart valve replacement).

• Registration Number: 2024-515998-94-00
• Lead Sponsor: Rigshospitalet

Brief Summary

The primary objective of this trial is to determine the efficacy of dexamethasone compared with placebo on the primary endpoint days alive outside hospital within 90 days in adult subjects undergoing elective or subacute isolated CABG, isolated AVR, or CABG plus any concomitant valve surgery. The coprimary objectives are to determine the efficacy of olanzapine versus placebo administered preoperatively, the efficacy of flow-targeted versus pressure-targeted hemodynamic management during CPB, and the efficacy of low tidal volume ventilation versus no ventilation during CPB, on the endpoint days alive outside hospital within 90 days in adult subjects undergoing elective or subacute isolated CABG, isolated AVR, or CABG plus any concomitant valve surgery.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-10-23
• Last Update Posted: 2024-10-23

Recruitment & Eligibility

• Status: Ongoing, recruiting
• Sex: Not specified
• Target Recruitment: 1200

Inclusion Criteria

Adult, i.e., above 18 years of age

Scheduled for CABG and/or AVR, irrespective of other concomitant valve surgery.

Exclusion Criteria

Acute surgery (i.e. off hours surgery)

Previous participation in the trial

Active infection, including bacterial, viral, and/or fungal infection

Known hepatic cirrhosis

Known severe thrombocytopenia with thrombocyte levels < 50 x 109/L

Known severe neutropenia with neutrocyte levels < 2 x 109/L

On the waiting list for a heart transplant

Type I diabetes

Known long QT syndrome

Known allergy for any of the included study drugs

Any condition, where participation in the study, in the investigator's opinion could put the subject at risk, confound the study results or interfere significantly with participation in the study

Recipient of any major organ transplant

Patients with extracardiac arteriopathy (assessed as part of the preoperative EuroSCORE) will be excluded from the intervention 'flowtargeted vs. pressure-targeted hemodynamic management during CPB'.

Obstructive hypertrophic cardiomyopathy, active myocarditis, constrictive pericarditis, untreated hypothyroidism or hyperthyroidism

Having received cytotoxic/cytostatic chemotherapy or radiation therapy for treatment of malignancy within the last 6 months

Clinical evidence of current malignancy except for basal or localized squamous cell carcinoma, cervical intraepithelial neoplasia or stable prostate cancer.

Known narrow-angle glaucoma

Known phenylketonuria

Pregnancy or currently breastfeeding

Known endocarditis at time of screening

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary endpoint will be number of days alive and outside hospital within 90 days after surgery.		The primary endpoint will be number of days alive and outside hospital within 90 days after surgery.

Secondary Outcome Measures

Name	Time	Method
Time in days to occurrence of any component in a composite secondary endpoint during follow-up: a) Death from any cause, b) Stroke, c) Acute kidney injury or d) New onset or worsening heart failure		Time in days to occurrence of any component in a composite secondary endpoint during follow-up: a) Death from any cause, b) Stroke, c) Acute kidney injury or d) New onset or worsening heart failure
Severe post-operative complications during index admission, defined as a Clavien-Dindo class of 3 to 5.		Severe post-operative complications during index admission, defined as a Clavien-Dindo class of 3 to 5.
Delirium during the first 7 days after surgery, defined as a positive Confusion Assessment Method for the ICU (CAM-ICU) score or a positive Confusion Assessment Method (CAM) score for the general wards		Delirium during the first 7 days after surgery, defined as a positive Confusion Assessment Method for the ICU (CAM-ICU) score or a positive Confusion Assessment Method (CAM) score for the general wards
Quality of Recovery-15 (QoR-15) score 3 days, or as soon as possible, after surgery		Quality of Recovery-15 (QoR-15) score 3 days, or as soon as possible, after surgery
90-day outcomes: Survival, Change in modified Rankin Scale (mRS) from baseline, Health-related quality of life (EQ-5D-5L), Change in self-perceived function "two simple questions" and Days alive outside ICU		90-day outcomes: Survival, Change in modified Rankin Scale (mRS) from baseline, Health-related quality of life (EQ-5D-5L), Change in self-perceived function "two simple questions" and Days alive outside ICU
180-day outcomes: Survival		180-day outcomes: Survival

Trial Locations

Locations (2)

Rigshospitalet; 🇩🇰 Copenhagen Oe, Denmark

Aarhus Universitet; 🇩🇰 Aarhus N, Denmark

Rigshospitalet

🇩🇰Copenhagen Oe, Denmark

Sebastian Wiberg

Site contact

35451710

sebastian.christoph.wiberg@regionh.dk