Possible Immuno-Modulatory Effect of Tocilizumab in Patients With Refractory Status Epilepticus.

Damanhour University

Status and phase: Unknown; Phase 3

Conditions: Epilepsy

Treatments: Drug: Tocilizumab Prefilled Syringe [Actemra]. propofole, phenobarbital, midazolam

Study type: Interventional

Funder types: Other

Identifiers

NCT05346666

34233/11/20

Details and patient eligibility

About

Recently, the pathogenesis of epilepsy is immuno-modulatory and neuro-inflammatory which is commonly activated in epileptogenic brain regions in humans and is clearly involved in animal models of epilepsy. Inflammatory mediators in the blood and molecular imaging of neuro-inflammation could provide diagnostic, prognostic, and predictive biomarkers for epilepsy, which will be instrumental for patient stratification in future clinical studies. Dysfunction of the blood-brain barrier (BBB) may be responsible for abnormal neuronal firing. Disruption of the BBB causes the leakage of serum protein and leucocyte invasion into the brain. These exogenous inflammatory mediators have the potential to lower seizure thresholds, which could alter channel sensitivity, neurotransmitter uptake or release, and glia-associated regulation of extracellular environments, such as potassium concentration.

Enrollment: 50 estimated patients

Sex: All

Ages: 15 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age: 15-75 years old.
• Gender: Male and female.
• Newly diagnosed refractory status epilepticus patients who are scheduled to receive anti-epileptic drugs.
• Patients with normal renal and hematological functions.

Exclusion criteria

• Old age >75 years old.
• Pregnant or lactating females.
• Severe renal impairment when GFR<30 ml/min.
• Hepatic patients ( not recommended with active hepatic disease or hepatic impairment specially when ALT or AST >3 times ULN).
• Neutropenia when neutrophil count <500 cells/mm3 due to increase the risk of infection.
• Thrombocytopenia when platelet count < 50000 cells/mm3.
• Patients take Immunosuppressant drugs.
• Cancer patient who taking chemotherapy.
• Patients with a known hypersensitivity to any of the used drugs.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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50 participants in 2 patient groups

Control Group

Active Comparator group

Description:

Group 1 received the conventional treatment for Status Epilepticus including propofol (loading dose is 3 to 5 mg/kg with maintenance of 1 to 15 mg/kg/h), phenobarbital (initial loading dose is 5 to 15 mg/kg over 1 hour. Infusion rates can be maintained at 0.5 to 15 mg/kg/h), and midazolam (a loading dose of 0.2 mg/kg is given with maintenance doses ranging between 0.05 and 2.0 mg/kg/h).

Treatment:

Drug: Tocilizumab Prefilled Syringe [Actemra]. propofole, phenobarbital, midazolam

Tocilizumab Group

Experimental group

Description:

Group 2 received the same treatment in group 1 in addition to tocilizumab that was initiated at a dose of 4mg/kg administered twice monthly with 1-week intervals for 3 months. A monthly dose (8mg/kg) of tocilizumab was added if needed.

Treatment:

Drug: Tocilizumab Prefilled Syringe [Actemra]. propofole, phenobarbital, midazolam