Early Sedation with Dexmedetomidine vs. Placebo in Older Ventilated Critically Ill Patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Monash University

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

Trial duration

7 Feb 2024 → ongoing

Decision date (initial)

2025-01-15

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Australian Government National Health and Medical Research Council

External identifiers

EU CT number

2022-501157-36-00

WHO UTN

U1111-1255-5885

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

1. To evaluate mortality among patients ≥ 65 years of age given early DEX as a primary sedative agent to verify the findings of the sub-group analysis in SPICE III trial (Early sedation with dexmedetomidine vs usual care in critically ill patients).

Secondary objectives 2

1. 2. To compare other key clinical outcomes with early sedation with DEX compared with placebo in the age group ≥ 65 years
2. 3. Explore possible mechanistic explanations for the observed effect in older patients in the SPICE III study.

Conditions and MedDRA coding

Critically ill patients who are dependent on high level medical care including mechanical ventilation, vasopressors and sedative/analgesic medication

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age ≥ 65 years
2. The treating clinicians believe that the patient will remain intubated and ventilated until the day after tomorrow (i.e. unlikely to be extubated the following day)
3. Intubated and receiving invasive mechanical ventilation in an intensive care unit
4. The patient requires immediate ongoing sedative medication for comfort, safety and to facilitate the delivery of life support measures.

Exclusion criteria 13

1. Has been intubated (excluding time spent intubated within an operating theatre or transport) for greater than 18 hours in an intensive care unit
2. Proven or suspected acute primary brain lesion such as traumatic brain injury, haemorrhage, stroke, or hypoxic brain injury
3. Proven or suspected spinal cord injury or other pathology that may result in permanent or prolonged weakness
4. Admission as a consequence of a suspected or proven drug overdose or burns
5. Administration of or need for ongoing neuromuscular blockade
6. A mean arterial blood (MAP) pressure that is less than 50 mmHg, despite adequate resuscitation and vasopressor support at time of randomization
7. Heart rate less than 55 beats per minute unless the patient is being treated with a beta-blocker, or a high grade atrio-ventricular block in the absence of a functioning pacemaker
8. Known sensitivity to dexmedetomidine
9. Acute fulminant hepatic failure
10. Receiving full time residential nursing care
11. Death is deemed both imminent and inevitable and either the attending physician, patient or substitute decision maker is not committed to active treatment
12. Underlying disease that makes survival to 90 days unlikely
13. Previously enrolled in the SPICE IV study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The study primary outcome is 90-day all-cause mortality.

Secondary endpoints 5

1. • Number of days alive and free of coma and delirium at 28 days
2. • Number of days alive and ventilator free at 28 days
3. • Major Adverse Kidney Events at 28 days (Mortality + Acute Kidney Injury > stage II, defined by Kidney Disease Improving Global Outcome (KDIGO) definition
4. • Duration of mechanical ventilation in survivors
5. • Hospital length of stay in survivors

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Monash University

Sponsor organisation

Monash University

Address

Wellington Road

City

Clayton

Postcode

3800

Country

Australia

Scientific contact point

Organisation

Monash University

Contact name

Yahya Shehabi

Public contact point

Organisation

Monash University

Contact name

Yahya Shehabi

Locations

5 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications