Dual Anti-glutamate Therapy in Super-refractory Status Epilepticus After Cardiac Arrest
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorUniversity of Milano Bicocca
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
EEG with periodic pattern (generalized periodic discharges; GPDs)
status epilepticus resolved after the first cycle of anesthetics + antiepileptics
pregnant women
Trial population
Patients with super-refractory status epilepticus after cardiac arrest, admitted to the Intensive Care Unit, with continuous EEG monitoring, presence of first-line favorable prognostic indicators (pupillary reflexes and N20 cortical responses bilaterally; absence of periodic EEG pattern). Outcomes will be also analyzed for the following pre-defined population: "Patients with favorable prognostic indicators": patients presenting 5 or more of the following: 1) presence of a pupillary reflex bilaterally; (2) presence of corneal reflex bilaterally; (3) presence of N20 cortical response bilaterally; (4) NSE \<68 ng/mL at 24-72 hours from ACC; (5) absence of periodic EEG patterns (GPDs); (6) absence of severe anoxic brain damage on neuroimaging
Trial design
Design model
Cohort
Time perspective
Retrospective
Treatments tested in this trial
Ketamine
Drug"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.
Any anti-epileptic and anesthetic therapy, excluding Ketamine and Perampanel
DrugAny antiseizure and anesthetic therapy according to usual clinical practice, excluding the two anti-glutamate drugs Ketamine and Perampanel
Treatment groups
80 Participants
are divided into 2 treatment groupsGroup A: Dual anti-glutamate therapy (DUAL)1 intervention
Group B: Control (OTHERS)1 intervention
Trial outcomes
Primary outcomes
1
Number of patients with resolution of status epilepticus
Number of patients with resolution of status epilepticus, not followed by relapse and without the use of additional antiepileptic drugs, evaluated over the entire period of stay in the Intensive Care Unit, in the two groups DUAL versus OTHERS
Time frame
Over the entire period of stay in the Intensive Care Unit (up to 30 days)Secondary outcomes
1
Number of patients with with time-locked resolution of status epilepticus
Number of patients with with resolution of status epilepticus 5 days after the start of therapy, not followed by relapse and without the use of additional antiepileptic drugs (only in the DUAL group)
Time frame
first 5 days after start of therapy2
Number of patients with early favorable neurological outcome
Number of patients with early favorable neurological outcome, defined as the patient's awakening (up to "command execution") during the stay in the Intensive Care Unit
Time frame
Over the entire period of stay in the Intensive Care Unit (up to 30 days)3
Number of patients with favorable long-term neurological outcome
Number of patients with favorable long-term neurological outcome, defined by a modified Rankin scale score ≤ 2 at 6 months (minimum score 0, maximum score 6; lower scores indicate better outcomes)
Time frame
6 months after cardiac arrest4
mortality in intensive care
mortality in intensive care
Time frame
Over the entire period of stay in the Intensive Care Unit (up to 30 days)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Milano Bicocca
Lead sponsor
Azienda Ospedaliera San Gerardo di Monza
Collaborator
Azienda Ospedaliero-Universitaria di Modena
Collaborator
Azienda Ospedaliera Universitaria Integrata Verona
Collaborator
Ospedale Centrale Bolzano
Collaborator
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Collaborator
Azienda Ospedaliero-Universitaria Careggi
Collaborator
Azienda Ospedaliero-Universitaria di Parma
Collaborator
Santa Chiara Hospital
Collaborator
Ospedale M. Bufalini Cesena
Collaborator
Azienda Ospedaliera Brotzu
Collaborator
Istituto Di Ricerche Farmacologiche Mario Negri
Collaborator
Source ClinicalTrials.gov