Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05335109 |
| Other study ID # |
NEXT |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
December 1, 2022 |
| Est. completion date |
November 29, 2024 |
Study information
| Verified date |
September 2022 |
| Source |
Negovsky Reanimatology Research Institute |
| Contact |
Oleg Grebenchikov, MD |
| Phone |
+79686494147 |
| Email |
oleg.grebenchikov[@]yandex.ru |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In the Russian Federation, ischemic cerebral infarction is recorded annually in more than
450,000 people. It is the second most common cause of death after coronary heart disease.
The 30-day mortality rate after an ischemic cerebral infarction is more than 25%, and during
the following year about half of the patients die. To date, all candidate neuroprotective
drugs tested in various clinical trials have demonstrated insufficient efficacy . Therefore,
the development of new approaches to the treatment of severe brain injuries of various
etiologies is one of the most important tasks of critical condition medicine.
Brain damage due to stroke triggers a number of pathophysiological reactions, which are based
on the accumulation of glutamate with the development of excitotoxicity. The effect of
glutamate on NMDA receptors is one of the main factors of neurodegenerative disorders.
Xenon is an anesthetic whose neuroprotective properties have been shown in many experimental
studies. Хenon inhalation after ischemia and reperfusion suppresses ischemic brain damage and
tPA-induced cerebral hemorrhages, and damage to the blood-brain barrier.
The most interesting is a randomized controlled trial performed by R. Laitio et al. (2016),
in which the use of xenon in combination with hypothermia in clinical practice was studied
for the first time. In patients who have undergone community-acquired cardiac arrest, xenon
inhalation at a concentration of 40 vol.% within 24 hours in combination with hypothermia,
led to less damage to the white matter of the brain than with patients using hypothermia
alone. The 6-month mortality rate was 27% in the xenon and hypothermia group and 35% in the
hypothermia group.
It is important to note that today, despite a large pool of convincing preclinical studies
proving the neuroprotective properties of xenon, there is not a single clinical study of its
use in ischemic stroke.
Therefore, the research objectives is to determine whether the strategy of using xenon-oxygen
mixture inhalation is better than oxygen-air mixture inhalation with respect to the change in
scores on the NIHSS, Rankin and Glasgow coma scales on day 7, the duration of stay in the ICU
and the frequency of nosocomial pneumonia.
Description:
In the Russian Federation, ischemic cerebral infarction is recorded annually in more than
450,000 people. It is the second most common cause of death after coronary heart disease.
The 30-day mortality rate after an ischemic cerebral infarction is more than 25%, and during
the following year about half of the patients die, which is more than 200,000 people. The
consequences of stroke belong to the first place among the causes of primary disability. No
more than 15% of those who have suffered a stroke return to work or fully perform their
previous household duties, and the rest, due to disability, need lifelong medical and social
rehabilitation. To date, all candidate neuroprotective drugs tested in various clinical
trials have demonstrated insufficient efficacy . Therefore, the development of new approaches
to the treatment of severe brain injuries of various etiologies is one of the most important
tasks of critical condition medicine.
Brain damage due to stroke triggers a number of pathophysiological reactions, which are based
on the accumulation of glutamate with the development of excitotoxicity. The effect of
glutamate on NMDA receptors is one of the main factors of neurodegenerative disorders.
Xenon is an anesthetic whose neuroprotective properties have been shown in many experimental
studies. However, the clinical part is still presented rather modestly. After it was
discovered that xenon is an inhibitor of NMDA receptors, it was shown that xenon can protect
neuronal cell cultures from damage caused by NMDA, glutamate, or oxygen-glucose deprivation.
It has been experimentally established that xenon is an inhibitor of tissue plasminogen
activator (tPA) and dose-dependent inhibits tPA-induced thrombolysis; xenon inhalation after
ischemia and reperfusion suppresses ischemic brain damage and tPA-induced cerebral
hemorrhages, and damage to the blood-brain barrier.
Exposure to xenon after transient ischemia in rats leads to a decrease in the volume of
infarction, depending on the concentration, exposure time and improvement of neurological
function 7 days after ischemia. To date, a role has been discovered in the implementation of
molecular mechanisms of xenon neuroprotection of double-pore potassium channels (TREK-1),
which provide a basic ion current that weakens neuronal excitability, thereby protecting
neurons from damage. The role of adenosine triphosphate (ATP)-sensitive potassium channels of
the plasmalemma in the realization of the protective properties of xenon is also discussed in
the scientific literature. It was shown that under in vitro conditions in the culture of
neurons, xenon protected them from damage caused by glucose and oxygen deprivation by
activating ATP-sensitive potassium channels in the plasmalemma. There is evidence of the
effect of xenon inhalation on the phosphorylation of glycogen synthase-3ß, a key enzyme of
the anti-apoptotic neuronal cascade, and an increase in the pool of enzymes involved in the
antioxidant protection of the brain. An experimental study showed a distinct
anti-inflammatory effect of this anesthetic, which consisted in an increase in the ability of
neutrophils to spontaneous apoptosis and a decrease in the expression of adhesion molecules
CD11b and CD66b on their surface after modeling an inflammatory reaction. Also, the
anti-inflammatory properties of xenon were shown when modeling traumatic brain injury in
vivo, when its exposure for 60 minutes caused a significant decrease in the expression of
pro-inflammatory genes NF-kB1 and NF-kB2, responsible for the synthesis of cytokines and
other molecules involved in inflammation. Considering that the inflammatory reaction that
forms in the first hours of ischemic brain damage largely determines the severity of its
further course, such an effect on neutrophils can reduce the severity of damage to nervous
tissue.
The most interesting is a randomized controlled trial performed by R. Laitio et al. (2016),
in which the use of xenon in combination with hypothermia in clinical practice was studied
for the first time. In patients who have undergone community-acquired cardiac arrest, xenon
inhalation at a concentration of 40 vol.% within 24 hours in combination with hypothermia,
led to less damage to the white matter of the brain than with patients using hypothermia
alone. The 6-month mortality rate was 27% in the xenon and hypothermia group and 35% in the
hypothermia group. However, the study was not powerful enough.
It is important to note that today, despite a large pool of convincing preclinical studies
proving the neuroprotective properties of xenon, there is not a single clinical study of its
use in ischemic stroke.
Therefore, the research objectives is to determine whether the strategy of using xenon-oxygen
mixture inhalation is better than oxygen-air mixture inhalation with respect to the change in
scores on the NIHSS, Rankin and Glasgow coma scales on day 7, the duration of stay in the ICU
and the frequency of nosocomial pneumonia.
