Clinical trial NCT04297345: Feasibility and Safety Study to Evaluate the Neuroprotective Effect of Hemodialysis in Acute Ischemic Stroke
Official title: Feasibility, Safety, Randomized, Controlled, Open-label Study to Evaluate the Neuroprotective Effect of Hemodialysis of Plasma Glutamate and Proinflammatory Cytokines in the Acute Phase of Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cerebrovascular Stroke
Keywords: hemodialysis neuroprotection
glutamate
proinflammatory cytokines
clinical trial
safety and efficacy
Lead sponsor: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Sponsor class: OTHER
First posted: 2020-03-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Controlled, Open-label

The active group will include patients with acute ischemic stroke who, in addition to conventional treatment (best possible medical treatment in patients admitted to a stroke unit), will undergo two hemodialysis sessions in the acute phase of stroke.

The control group will be composed of patients with similar clinical and demographic characteristics to whom only conventional medical treatment will be applied.
Primary purpose: TREATMENT

Brief summary: Hemodialysis is a therapeutic strategy used in subjects with chronic renal failure. Our working hypothesis is based on results published in experimental animal models of stroke where the investigators have demonstrated that peritoneal dialysis is an effective technique to reduce blood glutamate levels and reduce infarct volume.

The objective of this clinical trial is to evaluate the viability, safety and efficacy of hemodialysis in patients with acute ischemic stroke, proposing that it may have a) a potential neuroprotective effect by reducing the excitotoxic levels of glutamate and proinflammatory cytokines in blood and b) fewer technical problems than peritoneal dialysis to apply in usual clinical practice.

Detailed description: The reason for the present study is based on previous data from the group that demonstrated the following results: a) The decrease in plasma Glu, by peritoneal dialysis (PD), reduces the size of the brain infarct in a model of focal cerebral ischemia in rats; b) PD is effective in reducing plasma Glu levels in patients with chronic renal failure; c) PD is a safe and well tolerated procedure in patients with ischemic stroke in the acute phase, however, it was not a viable procedure in our conditions, due to the malfunction of the automatic system that made it difficult for the inclusion sessions and dialysate extraction and the difficulty for the collaboration of this type of patient with the procedure; d). The increase in the median concentration of Glu after cerebral infarction was reduced to 46% after PD.

Based on our previous results, the investigators believe that hemodialysis may have fewer technical problems than PD and serve as a neuroprotection technique by lowering the levels of Glu and proinflammatory cytokines in blood. To do this, the investigators establish the following objectives: a) To evaluate the feasibility and safety of a hemodialysis procedure in patients with acute ischemic stroke compared to a control group; b) To analyze the clinical benefit of hemodialysis estimated by the volume of the infarction and the neurological and functional situation of the patients; and c) To measure the levels of glutamate and proinflammatory cytokines in plasma and dialysate samples. For this, a single-center, randomized, open-label, controlled study has been designed with a group of patients with ischemic stroke who receive conventional treatment (N=10) or conventional treatment + 2 hemodialysis sessions (N=10) in the acute phase of the stroke (Phase IIa clinical trial with medical device).

Eligibility criteria: Inclusion Criteria:

1. Patients older than 18 years.
2. Acute ischemic stroke confirmed by multimodal CT due to occlusion of a large caliber artery in the intracranial internal carotid and / or M1 and / or tandem half-portion cerebral artery.
3. ASPECTS between 4-10 in the CT scan without contrast of admission.
4. Patients should be treated by mechanical thrombectomy, with or without prior treatment with rtPA-iv, with a final \>=TICI 2b result.
5. Patients to whom pharmacological thrombolytic treatment (rt-PA) and/or mechanical thrombectomy is applied and their NIHSS is ≥ 8 at 60 minutes having completely finished the reperfusion treatment performed.
6. \<12 h from the onset of symptoms to the start of treatment by hemodialysis or the inclusion in the arm of conventional medical treatment. Those patients with uncertain or unknown time of onset of symptoms may be included in the study provided that the same in the multimodal CT scan is\> = 50%
7. The participants have granted their consent.

Exclusion Criteria:

1. Patients with prior important functional dependence (mRS\> 3);
2. Presence of a minor neurological deficit (NIHSS scale\< 8 at the time of randomization);
3. Coma state;
4. Ischemic stroke of posterior territory;
5. Hemorrhagic stroke in the neuroimaging test performed at the beginning;
6. Pregnancy or lactation (urinalysis will be performed prior to randomization in women of childbearing age);
7. Hematological, infectious, inflammatory or chronic neoplastic diseases known at the time of treatment;
8. Patients with severe chronic renal failure on hemodialysis (stage 5D)
9. Severe liver disease (ascites or coagulopathy, for example);
10. Any serious, advanced or terminal illness with an expected life expectancy of less than 6 months;
11. Any comorbidity situation that, at the discretion of the investigator, may prevent the patient from completing the study;
12. Stroke or myocardial infarction in the previous 90 days;
13. Platelet count \<100,000 / mm3;
14. Anticoagulated patients who, in the opinion of the Nephrologist, the establishment of the central route for performing hemodialysis poses a high risk of bleeding;
15. Participation in another clinical trial in the previous 90 days.

Primary outcomes:
measure: Primary Safety Endpoint: Percentage estimation of mortality
timeFrame: Day 90
measure: Primary Safety Endpoint: Number of adverse effects
timeFrame: Day 90
measure: Primary Safety Endpoint: Percentage of participants with early neurological impairment
timeFrame: Day 7
measure: Primary Safety Endpoint: Percentage of participants with symptomatic bleeding transformation
timeFrame: Day 3
measure: Feasibility of hemodialysis procedure in stroke: participant adherence to hemodialysis procedure.
timeFrame: Day 3
measure: Feasibility of hemodialysis procedure in stroke: Time of intervention
timeFrame: Day 3
Secondary outcomes:
measure: Efficacy of the first haemodialysis in the reduction of plasma Glu
timeFrame: Hour 0, hour 0.5, hour 3, hour 3.5
measure: Efficacy of the first haemodialysis in the reduction of plasma pro-inflammatory cytokines
timeFrame: Hour 0, hour 0.5, hour 3, hour 3.5
measure: Efficacy of the second haemodialysis in the reduction of plasma Glu
timeFrame: Hour 0, hour 0.5, hour 3, hour 3.5
measure: Efficacy of the second haemodialysis in the reduction of plasma pro-inflammatory cytokines
timeFrame: Hour 0, hour 0.5, hour 3, hour 3.5
measure: Efficacy of haemodialysis in the reduction of infarct volume
timeFrame: Day 1, day 3
measure: Percentage of participants with favourable evolution of the neurological deficit
timeFrame: Day 7
measure: Percentage of participants with good functional recovery as assessed by the Modified Rankin Scale
timeFrame: Month 3.
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: José Vivancos Mora, MD., PhD
Study officials:
affiliation: Instituto de Investigación Hospital la Princesa
name: José Vivancos, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: