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ID
Source
Brief title
Health condition
Postanoxic encephalopathy, postanoxic, coma after cardiac arrest, ghrelin administration, neuroprotection
Sponsors and support
Clinical neurophysiology
Drienerlolaan 5
7522NB Enschede
Intervention
Outcome measures
Primary outcome
We aim to measure safety and efficacy of intravenous treatment with acyl-ghrelin to promote cerebral recovery in comatose patients after cardiac arrest. Safety will be monitored throughout hospitalization and during follow-up using all AEs reported, and by interim analyses by an independent DSMB. Efficacy will be measured by the primary outcome measure, i.e. functional recovery as measured by the Cerebral Performance Category (CPC) scale at six months after cardiac arrest.
Secondary outcome
To estimate efficacy of ghrelin to modify:
1. Case fatality
2. Time to awaken (time interval between resuscitation and Glasgow Coma Scale (GCS) score of 14)
3. Long term outcome: CPC and cognitive functioning at 12 months
4. Cardiovascular measures:
• Mean arterial blood pressure day 1-7 (mean, highest, lowest)
• Heart rate day 1-7 (mean, highest, lowest)
• Arrhythmia day 1-7: yes / no. If yes: type of arrhythmia
• Cumulative dose of vasopressive medication day 1-7
• Cumulative dose of inotropic medication day 1-7
• Sequential Organ Failure Assessment score day 1-7
• Kidney function day expressed as GFR day 1-7
• CVVH day 1-7: yes / no
• Assist devices day 1-7: yes / no
5. Biomarkers
• Cardiac: troponine and CK / CK-MB ratio at day 0, 1, 2 or 3
• Neurological: NSE day 1, 2, 3
• Endocrinological: cortisol, growth hormone, prolactine, ACTH, IGF-1 day 1, 2, 3
6. Gastro-intestinal: gastric residual volume (day 1-7, during ICU admission)
Background summary
Rationale: Approximately half of all comatose patients after cardiac never regains
consciousness because of severe postanoxic encephalopathy. The other half may be left
with cognitive or motor disturbances. Currently, there is no treatment to promote cerebral
recovery. Treatment with acyl-ghrelin improved functional recovery under experimental in
vivo and in vitro conditions, and decreased histologically measured neuronal damage.
Ghrelin has been tested in over one hundred human studies, including studies in healthy
volunteers and patients with cardiopulmonary diseases, neuro-endocrine diseases,
psychiatric diseases, and neurodegenerative diseases. Serious adverse events were
extremely rare and difficult to attribute to ghrelin administration
Objective: First, we aim to estimate safety and efficacy of intravenous treatment with acyl-
ghrelin to promote cerebral recovery in comatose patients after cardiac arrest. Second, we
will estimate efficacy of ghrelin to modify case fatality, time to awaken, long term (cognitive)
outcome, and cardiovascular outcomes, including blood pressure, treatment with inotropic
medication, treatment with vasopression and cardiac biomarkers.
Study design: This will be a phase 2 multicenter, double blind, placebo controlled
randomized clinical trial.
Study population: Comatose patients (GCS score of 8 or lower) after cardiac arrest and
successful cardiopulmonary resuscitation, admitted to intensive care units of participating
hospitals, will be included within 12 hours after resuscitation.
Intervention Intravenous treatment with acylated ghrelin 600micrg twice daily for 1 week vs.
placebo.
Main study parameters/endpoints: The primary outcome measure will be functional
outcome as expressed as the score of the cerebral performance category (CPC) at 6
months.
Study objective
Ghrelin administration in comatose patients after cardiac arrest is safe, causes no serious adverse events relatable to ghrelin use and it improves functional recovery in these patients.
Study design
Case fatality
Time to awaken
Cardiovasculair measures: day 0-7
Venous blood samples: day 0, 1, 2, 3
CPC scores: after 3 en 6 months
Neuropsychological examination: after 12 months
Gastric residual volume: day 0-7
Intervention
Intravenous treatment with acylated ghrelin 600micrg twice daily for 1 week vs. placebo.
J. Hofmeijer
Wagnerlaan 55
Arnhem 6815 AD
The Netherlands
jhofmeijer@rijnstate.nl
J. Hofmeijer
Wagnerlaan 55
Arnhem 6815 AD
The Netherlands
jhofmeijer@rijnstate.nl
Inclusion criteria
In order to be eligible to participate in this study a subject must meet the following criteria:
- Age ≥18 years
- Out of hospital cardiac arrest
- Successful cardiopulmonary resuscitation
- Return of spontaneous circulation ¡Ü12 hours ago
- GCS score on admission ≤ 8 or suspected coma in patients who are sedated
- Admission to intensive care unit
- Hemodynamic and respiratory stability as determined by the treating intensive care physician, with the minimum requirement of mean arterial pressure > 65 mmHg. Treatment with inotropes, vasopressors or IABP is allowed.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Age <18 years
- A known progressive neurological disease
- Expected death within 48 hours
Design
Recruitment
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| NTR-new | NL7155 |
| NTR-old | NTR7354 |
| Other | ZonMW : 951 05001 |