The primary objective is to investigate the feasibility and the safety of heliox administration, a gaseous mixture of 79% helium en 21% oxygen, for 8 hours in acute ischemic stroke.
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main clinical outcome is the change in neurological deficits between subjects
and controls quantified by the National Institute of Health Stroke Scale
(NIHSS) at 4 hours. Improvement is defined as a decrease of 4 or more points on
the NIHSS.
For safety analysis, clinical deterioration - defined as a decrease on the
Glasgow Coma Scale of more than 2 points and/or a increase of 4 or more points
on NIHSS - is primary outcome.
Secondary outcome
Secondary clinical measures are NIHSS scores at 24 hours, 1 week and 3 months
and level physical function measured by modified Rankin Scale (mRS) at 3
months. Independency (mRS <= 2) is considered as good outcome, whereas
dependency (mRs 3 -5) as bad.
Secondary safety outcomes are death by any cause and total and specific serious
adverse events. One defined specific serous adverse event is the occurrence of
symptomatic intracerebral haemorrhage. This event is regarded as symptomatic
when a decline in clinical performance in opinion to the clinical investigator
is related to the presence of these findings on a subsequently performed
CT-scan.
The final infarct size on CT-scan at 1 week related to the total amount of
tissue at risk volume on baseline CT-Perfusion scan is an outcome measure
considered as a signal of efficacy. Other secondary outcomes are the occurrence
of hemorrhagic transformation of infarcted tissue and final infarct size
demonstrated on the 1 week non-enhanced CT. Experienced discomfort from the
face mask and/or Helontix Vent is another secondary outcome.
Background summary
In acute stroke therapy treatment with rt-PA thrombolysis within 3 hours showed
a favourable outcome. Because of its small time window only a minority of
stroke patients is eligible for this treatment. Therefore, strategies that
arrest the transition from the hypoperfused but still viable penumbra to
infarction are necessary. Numerous experimental studies and clinical trials
assessing neuroprotective effects in ischemic stroke have been performed, but
failed to show convincing results.
One hypothesis of this failure is that in absence of oxygen neuronal cells take
up nitrogen in the mitochondria. As reperfusion - by thrombolysis or
spontaneous recanalization - occurs, an intracellular *nitrogen lock* prevents
oxygen to be taken up in the penumbra and ischemia will turn out into
infarction. By replacing nitrogen with another gas in the air inhaled this
intracellular nitrogen can be washed out before reperfusion. Partly due to
methodogical shortcomings, 100% oxygen therapy studies have never conclusive
positive results. Helium, an inert gas, has a lower density and diffuses more
rapidly in comparison with oxygen. These properties could be of interest in
egressing nitrogen from the mitochondria and secondly, helium might serve as a
tissue oxygen facilitator. An in vivo experiment tested the nitrogen washout
hypothesis in ischemic stroke and showed promising results with 100% oxygen and
even better results with helium. In cardio protection studies noble gas xenon
has inhibitory effects on the adhesive properties of the endothelium. As helium
lacks side effects and can be administered easily, it is a possible
neuroprotective option which should be further investigated as a first-step
treatment in acute ischemic stroke. Supported by experimental data on the use
of helium in acute ischemic stroke, we want to investigate the safety and
feasability of helium as a neuroprotective agent in acute ischemic stroke.
Study objective
The primary objective is to investigate the feasibility and the safety of
heliox administration, a gaseous mixture of 79% helium en 21% oxygen, for 8
hours in acute ischemic stroke.
Study design
Monocenter, prospective, randomized controlled safety and feasability study
Intervention
Eligible patients with ischemic stroke are randomized to receive either heliox
for 8 hours via a tight sealed face mask upon regular stroke care or regular
stroke care alone. Clinical outcome will be evaluated at baseline, at 4 hours,
24 hours at 1 week and at 3 months follow up.
Study burden and risks
As helium lacks relevant side effects no risks are associated with the
application and there is a possibility of neuroprotection. Study subjects are
wearing a face mask for 4 hours. Study subjects and controls will undergo a
brain CT-Perfusion scan at baseline and at 4 hours and a non-enhanced brain CT
scan at 1 week. Study-related radiation exposure is a negligible risk due to
the low dose exposure.
An outpatient department visit at 3 months makes an appeal to a subject*s
willingness.
Rijksstraatweg 1
1261 AN Blaricum
Nederland
Rijksstraatweg 1
1261 AN Blaricum
Nederland
Listed location countries
Age
Inclusion criteria
age >= 18 years;
clinical anterior circulation ischemic stroke;
< 12 hours of witnessed symptom onset
National Institutes of Health Stroke Scale (NIHSS) score >= 4;
pre-admission modified Rankin scale (mRS, dutch version) <= 1;
Visual estimation of penumbra/infarct ratio > 20%
Exclusion criteria
eligible for rt-PA thrombolysis;
inability to obtain written informed consent;
legal incapacity
medically instable (blood pressure >230/120 or <100/60 mmHg, pulse > 120 bpm, mechanical ventilation needed, body temperature above 39*C)
intracerebral hemorrhage on admission non-enhanced CT;
rapidly improving neurological deficits;
pregnancy;
impaired renal function (serum creatinin levels > 130 µmol/l)
allergic to contrast agent;
use of anticoagulation drugs or coagulopathy (PTT > 1.5 times control)
use following nephrotoxic medications: aminoglycosids, amfoterecine B or cisplatin
contra-indication or intolerance to any used substance;
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-001737-10-NL |
| CCMO | NL21743.003.08 |
| OMON | NL-OMON25537 |