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

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.

Conditions

• Status Epilepticus
• Cardiac Arrest

Interventions

DRUG

Ketamine

"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.

DRUG

Any 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

Sponsors & Collaborators

• Azienda Ospedaliera San Gerardo di Monza

  collaborator OTHER

• Azienda Ospedaliero-Universitaria di Modena

  collaborator OTHER

• Azienda Ospedaliera Universitaria Integrata Verona

  collaborator OTHER

• Ospedale Centrale Bolzano

  collaborator OTHER

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

  collaborator OTHER

• Azienda Ospedaliero-Universitaria Careggi

  collaborator OTHER

• Azienda Ospedaliero-Universitaria di Parma

  collaborator OTHER

• Santa Chiara Hospital

  collaborator OTHER

• Ospedale M. Bufalini Cesena

  collaborator OTHER

• Azienda Ospedaliera Brotzu

  collaborator OTHER

• Istituto Di Ricerche Farmacologiche Mario Negri

  collaborator OTHER

• University of Milano Bicocca

  lead OTHER

Principal Investigators

• Simone Beretta, MD, PhD · University of Milano Bicocca

• Matteo Pozzi, MD · Fondazione IRCCS Gerardo dei Tintori Monza

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-01-15

Primary Completion

2025-09-30

Completion

2025-09-30

Countries

• Italy

Study Locations