RecruitingNCT05756621

Dual Anti-glutamate Therapy in Super-refractory Status Epilepticus After Cardiac Arrest

SUPER-refractory Status Epilepticus After Cardiac Arrest: a Multicenter, Retrospective, Cohort Study of Dual Anti-glutamate Therapy With Ketamine and Perampanel


Sponsor

University of Milano Bicocca

Enrollment

80 participants

Start Date

Jan 15, 2022

Study Type

OBSERVATIONAL

Conditions

Summary

Status epilepticus (SE) is found in 20-30% of patients in coma after cardiac arrest, is often refractory to medical therapy and is considered a negative prognostic factor. Intensity and duration of treatment of refractory and super-refractory post-anoxic SE pose the ethical dilemma between futility of treatments and, conversely, their premature suspension. A recent study by the Epilepsy Center of the San Gerardo Hospital has shown that patients with super-refractory post-anoxic SE and favorable prognostic indicators can achieve a good functional outcome in more than 40% of cases, if treated with intensive and protracted therapy. However, there is profound uncertainty about the best combination of antiseizure medications and anesthetics to use in this condition. A combined anti-glutamatergic therapy with ketamine (anti-NMDA receptor) and perampanel (anti-AMPA receptor), aimed at counteracting the excitotoxicity linked to global cerebral ischemia, could be particularly effective in the treatment of super-refractory SE with post-anoxic etiology. Preliminary results in the first 26 patients treated in the Coordinating Center of the project indicate that this therapy appears safe and highly effective (80% SE resolution, 40% good neurological outcome). The aim of the SUPER-CAT study is to investigate the efficacy and safety of combined therapy with ketamine and perampanel (dual anti-glutamatergic therapy) in patients with post-anoxic super-refractory status epilepticus, compared to other therapies, using a multi-centre, retrospective, cohort study design.


Eligibility

Min Age: 18 Years

Inclusion Criteria6

  • age ≥ 18 years
  • patients in coma after cardio-circulatory arrest (CCA) admitted to the Intensive Care Unit and treated with target temperature management (TTM) for the first 24 hours
  • initiation of continuous electroencephalographic (cEEG) monitoring within 24-36 hours of CCA
  • diagnosis of super-refractory status epilepticus, relapsed after the first cycle of anesthetics (lasting \> 24 hours) and antiepileptic therapy, defined according to the international Salzburg criteria9
  • presence of pupillary reflex present bilaterally
  • presence of N20 cortical response present bilaterally

Exclusion Criteria3

  • EEG with periodic pattern (generalized periodic discharges; GPDs)
  • status epilepticus resolved after the first cycle of anesthetics + antiepileptics
  • pregnant women

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Interventions

DRUGKetamine

"Dual anti-glutamatergic therapy" (DUAL) intervention group: patients who received ketamine as a continuous i.v. for 3 days (induction dose 1.5-3 mg/kg, followed by maintenance dose 2-10 mg/kg/h; dose adjustment according to EEG target of "ketamine pattern") + oral perampanel via nasogastric tube for 5 days (12 mg if weight \> 60 kg; 9 mg if weight 50-60 kg; 6 mg if weight \< 50 kg), followed by gradual reduction according to clinical evolution.

DRUGAny anti-epileptic and anesthetic therapy, excluding Ketamine and Perampanel

Any antiseizure and anesthetic therapy according to usual clinical practice, excluding the two anti-glutamate drugs Ketamine and Perampanel


Locations(10)

ASST Spedali Civili Brescia

Brescia, BS, Italy

Ospedale Centrale di Bolzano

Bolzano, BZ, Italy

Ospedale G. Brotzu

Cagliari, CA, Italy

Ospedale M. Bufalini

Cesena, FC, Italy

AOU Careggi

Florence, FI, Italy

Fondazione IRCCS San Gerardo dei Tintori Monza

Monza, MB, Italy

Azienda Ospedaliero-Universitaria di Modena

Modena, MO, Italy

Azienda Ospedaliero-Universitaria di Parma

Parma, PR, Italy

Ospedale Santa Chiara Trento

Trento, TN, Italy

Azienda Ospedaliero-Universitaria Integrata di Verona

Verona, VR, Italy

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NCT05756621


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