The primary objective of this study is to determine whether targeted therapeutic mild hypercapnia (TTMH) improves neurological outcome at 6 months compared to standard care (targeted normocapnia) (TN).
ID
Source
Brief title
Condition
- Cardiac arrhythmias
- Encephalopathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure for this study is the proportion of patients with a
favourable neurological outcome at 6 months as assessed using the GOSE.
Secondary outcome
(I) Mortality at ICU and hospital discharge and at 6 months after
randomisation.
(II) Functional recovery as measured by the proportion of patients with a
favourable functional outcome at 6 months after randomisation as assessed using
the modified Rankin scale and the Cerebral Performance Category
(III) Cognitive functional recovery assessed at 6 months after randomisation
using the Montreal Cognitive Assessment; Informant Questionnaire on Cognitive
Decline; Symbol Digit Modalities Test and 30-second chair test.
(IV) Quality of life at 6 months after randomisation assessed by the five
domains of Mobility, Self-care, Usual Activity, Pain/discomfort, and
Anxiety/Depression of the EQ-5D-5L scale.
(V) Safety as determined as the proportion of adverse events occurring between
groups as reported by treating clinicians.
(VI) A health economic assessment will be performed to evaluate differences in
costs for hospital length of stay and destination at discharge for patients
allocated to TTMH and standard care (TN).
Background summary
Cardiac arrest is a common and catastrophic event. Out-of-hospital cardiac
arrest has an estimated incidence of approximately 1 per 1,000 persons per year
with mortality rates varying between 87 to 94%. Once admitted to an Intensive
Care Unit (ICU), survival is still unacceptably low at approximately 40% and
has remained unchanged over the last decade. These ICU mortality is mainly due
to severe cerebral injury sustained during CPR and after return of circulation
(reperfusion injury). Accordingly, while the initial problem is cardiac in
nature, after ICU admission, the dominant reason for such dismal outcomes is
neurological injury. Thus, a better neurological outcome is the logical and
dominant therapeutic goal in a population where more than half are of working
age. The brain is particularly susceptible to damage following return of
spontaneous circulation with reperfusion injury and inflammation both of which
may contribute to subsequently increased vascular resistance and sustained
hypoperfusion. PaCO2 is the major determinant of cerebral blood flow in man.
The in this study proposed therapeutic CO2 target was simple, easy to aim for,
with no signs of harm and cost free. Together with the large epidemiological
study, double crossover physiological study and phase II trial already
conducted, there is now epidemiological, biological, physiological, and
supportive clinical data suggesting that TTMH can deliver significant outcome
improvements in resuscitated cardiac arrest patients admitted to ICU. These
findings strengthen the need to perform a larger phase III trial to address the
question of whether targeting mild therapeutic hypercapnia improves
patient-centred outcomes in resuscitated cardiac arrest patients admitted to
the ICU. Thus, a larger definitive phase III trial is needed now.
Study objective
The primary objective of this study is to determine whether targeted
therapeutic mild hypercapnia (TTMH) improves neurological outcome at 6 months
compared to standard care (targeted normocapnia) (TN).
Study design
This a phase III multi-centre, randomised, parallel-group, controlled trial in
resuscitated cardiac arrest patients who are admitted to the intensive care
unit.
Intervention
targeted therapeutic mild hypercapnia (TTHM) aiming at a PaCO2 of 50-55 mmHg
during 24 hours versus standard care
Study burden and risks
Burden and risks associated with participation in this study are very small.
Patients randomized to the intervention arm might have a benefit of the
treatment.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
1. Adult (age *18 years or older)
2. Out-of-hospital cardiac arrest of a presumed cardiac or unknown cause
3. Sustained ROSC * defined as 20 minutes with signs of circulation without the need for chest compressions
4. Unconscious (FOUR-score motor response of <4, not able to obey verbal commands after sustained ROSC)
5. Eligible for intensive care without restrictions or limitations
6. Within <180 minutes of ROSC
Exclusion criteria
1. Unwitnessed cardiac arrest with an initial rhythm of asystole
2. Temperature on admission <30 C
3. On ECMO prior to ROSC
4. Obvious or suspected pregnancy
5. Intracranial bleeding
6. Severe chronic obstructive pulmonary disorder (COPD) with long-term home oxygen therapy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT03114033 |
| CCMO | NL62674.018.17 |