Table 1 Inclusion and exclusion criteria

Coma with reduced consciousness with GCS < 8

Lasting at least 72 h, not otherwise explained

Age ≥ 18 years

at the time of signing the informed consent.

Inconspicuous EEG and ECG

-

In woman of child bearing potential: pregnancy excluded

By measurement of human chorionic gonadotropin (hCG) in serum before start of study medication

Informed consent

As subjects per definition suffer from reduced consciousness and therefore are not in a position to provide informed consent themselves, prior to any study related procedures, the patient’s legal representative has to give written informed consent. The informed consent of the patient will be sought retroactively as soon as possible.

Exclusion criteria

Reduced consciousness, otherwise sufficiently explained

Such as reduced consciousness due to status epilepticus, hyperglycemia, electrolyte imbalance, hyperkaliemia, akinetic crisis in Parkinson’s Disease or Delirium (Intensive Care Delirium Screening Checklist (ICDSC) > 4 or > 5 in aphasic patients)

Age < 18 years

-

Participation in other interventional study

Participation in an observational trial is acceptable

History of epileptic seizures/status epilepticus

-

Women during pregnancy and lactation

-

History of hypersensitivity to the investigational medicinal product

Or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product

Concomitant therapy with memantine

-

Severe uncompensated heart failure (NYHA IV)

E.g., due to cardiomyopathy or myocarditis

Atrioventricular block (AV block) second-degree and third-degree

-

Known bradycardia (below 55 beats/minute)

-

Known long QT interval (QTc according to Bazett > 420 ms) or recognizable U-waves or congenital QT syndrome in the Family history

-

History of serious ventricular arrhythmias, including torsade de pointes

-

Hypokalemia or hypomagnesemia

-

Concomitant therapy with Budipine or other QT-prolonging drugs

Class IA (quinidine, disopyramide, procainamide) and III (amiodarone, sotalol) antiarrhythmic drugs, antipsychotics (thioridazine, chlorpromazine, haloperidol, pimozide), tri- and tetracyclic antidepressants (amitriptyline), antihistamines (astemizole, terfenadine), macrolide antibiotics (erythromycin, clarithromycin), gyrase inhibitors (sparfloxacin), azole antifungals and other medicines such as halofantrine, cotrimoxazole, pentamidine, cisapride, bepridil

Impaired renal function, measured by glomerular filtration rate (GFR) < 10 ml/min

Impaired renal function will necessitate dose adjustment (see Table 3).