Feasibility and Safety Study to Evaluate the Neuroprotective Effect of Hemodialysis in Acute Ischemic Stroke

NCT04297345 | Unknown

• 1 other identifier: JVM-HD-19
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Cerebrovascular Stroke

Keywords

hemodialysis neuroprotection; glutamate; proinflammatory cytokines; clinical trial; safety and efficacy

Outcome Measures

Primary Outcomes (6)

• Primary Safety Endpoint: Percentage estimation of mortality

  Reported here is the percentage of participants who died due to any cause during the study. Mortality will be compared between randomized groups in an intention-to-treat fashion

  Day 90

• Primary Safety Endpoint: Number of adverse effects

  An adverse event (AE) is defined as an undesirable medical occurrence in a participant of clinical research that does not necessarily have a causal relationship with this treatment. An AE can be a sign, symptom, laboratory finding, or result of an abnormal test. Adverse effects number will be compared between randomized groups in an intention-to-treat fashion

  Day 90

• Primary Safety Endpoint: Percentage of participants with early neurological impairment

  Early neurological impairment: Increase of 4 or more points on the NIHSS scale during the first 24 hours after treatment. The National Institutes of Health Stroke Scale, or NIH Stroke Scale (NIHSS) is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0. NIHSS score will be compared between randomized groups in an intention-to-treat fashion

  Day 7

• Primary Safety Endpoint: Percentage of participants with symptomatic bleeding transformation

  The incidence rate of intracranial hemorrhages on follow-up CT. The incidence rate will be compared between randomized groups in an intention-to-treat fashion

  Day 3

• Feasibility of hemodialysis procedure in stroke: participant adherence to hemodialysis procedure.

  The study will be considered viable if the percentage of patients who complete their hemodialysis procedure is equal to or greater than 70%.

  Day 3

• Feasibility of hemodialysis procedure in stroke: Time of intervention

  The study will be considered viable if, in at least 80% of patients, the time from randomization to the start of the hemodialysis treatment is not more than 2h.

  Day 3

Secondary Outcomes (7)

• Efficacy of the first haemodialysis in the reduction of plasma Glu

  Hour 0, hour 0.5, hour 3, hour 3.5

• Efficacy of the first haemodialysis in the reduction of plasma pro-inflammatory cytokines

  Hour 0, hour 0.5, hour 3, hour 3.5

• Efficacy of the second haemodialysis in the reduction of plasma Glu

  Hour 0, hour 0.5, hour 3, hour 3.5

• Efficacy of the second haemodialysis in the reduction of plasma pro-inflammatory cytokines

  Hour 0, hour 0.5, hour 3, hour 3.5

• Efficacy of haemodialysis in the reduction of infarct volume

  Day 1, day 3

Study Arms (2)

hemodialysis group

EXPERIMENTAL

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 for a period of about 3 hours each session in the acute phase of stroke. The investigators will perform a conventional and heparin-free hemodialysis using high-flow dialyzers to avoid possible adverse (allergic) reactions with polysulfones containing other dialyzers.

Device: Hemodialysis

control group

NO INTERVENTION

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

Interventions

Hemodialysis DEVICE

Blood enters the extracorporeal circuit from the arterial line of the femoral catheter. For this the investigators use a pump integrated in the monitor, equipped with control systems, exerting a negative pressure. Subsequently, it enters the dialyzer through the internal part of the capillaries (porous), producing a passive exchange of inflammatory and oxidative substances (such as cytokines) with the dialysis fluid, which also circulates through the dialyzer, but through the external part of the capillaries. Blood is returned to the patient, through the venous line of the catheter, with a lower concentration of cytokines after passing through the dialyzer. This circuit is repeated continuously during the 3 hours of the procedure to ensure maximum clearance of glutamate and interleukins, among other substances.

Also known as: extracorporeal blood purification technique

hemodialysis group

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients older than 18 years.
• 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.
• ASPECTS between 4-10 in the CT scan without contrast of admission.
• Patients should be treated by mechanical thrombectomy, with or without prior treatment with rtPA-iv, with a final \>=TICI 2b result.
• 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.
• The participants have granted their consent.

You may not qualify if:

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

Sponsors & Collaborators

• Fundación de Investigación Biomédica - Hospital Universitario de La Princesa: lead

Study Sites (1)

José Vivancos Mora, MD., PhD

Madrid, 28006, Spain

RECRUITING

MeSH Terms

Conditions

Stroke

Interventions

Renal Dialysis

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Renal Replacement Therapy; Therapeutics; Sorption Detoxification

Study Officials

• José Vivancos, MD,PhD

  Instituto de Investigación Hospital la Princesa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Monica Sobrado, PhD

CONTACT

+34915202416; sobrado.m@gmail.com

Carmen Ramos, MD

CONTACT

+34915202416; cramosmartin90@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Health personnel not belonging to the research team will be responsible for randomizing patients with a table of random numbers in a proportion 1 control: 1 dialysis. The identity of the treatment will remain masked for the analysis of clinical and laboratory data: The researchers will not know the determination of the concentration of Glu and proinflammatory cytokines in the serum and in the dialysate fluid of the patients until the end of the study, once the database is closed and the randomization codes are opened. Neuroimaging tests Multimodal CT and simple CT) will be evaluated by a single Neuroradiologist of the Radiology Service of the Hospital de La Princesa, blind to the clinical and biological variables of the patients.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 4, 2020
• First Posted: March 5, 2020
• Study Start: January 1, 2021
• Primary Completion: November 1, 2022
• Study Completion: December 1, 2022
• Last Updated: January 3, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)