Evaluation of Early Administration of Levetiracetam in the Prevention and Treatment Encephalopathy in Septic Shock: Randomized, Double-blind, Placebo-controlled Trial (KiSS)

Assistance Publique - Hôpitaux de Paris

Status and phase: Not yet enrolling; Phase 3

Conditions: Septic Shock

Treatments: Drug: Levetiracetam IV; Other: Placebo control

Study type: Interventional

Funder types: Other

Identifiers

NCT06851078

APHP200068

Details and patient eligibility

About

Sepsis-associated encephalopathy is associated with high mortality rates and long-term neuropsychiatric disorders. Currently, there is no specific treatment for sepsis-associated encephalopathy. Levetiracetam, a broad-spectrum antiepileptic widely used in intensive care units, has neuroprotective properties. We propose the KiSS study, a multicenter, prospective, randomized, double-blind trial with two arms, evaluating the effect of levetiracetam treatment for seven days during septic shock on the occurrence and duration of sepsis-associated encephalopathy.

Enrollment: 280 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

• Aged 18 years or older

• Hospitalized in intensive care for less than 96 hours

• Presenting with septic shock evolving for less than 24 hours defined by:

  1. Clinically or microbiologically documented infection and
  2. SOFA score ≥ 2 or an increase in SOFA score ≥ 2 points if organ dysfunction was present before the infection and
  3. Need for vasopressor administration to maintain a mean arterial pressure ≥ 65mmHg and
  4. Lactate level > 2mmol/L (18mg/dL) despite adequate fluid resuscitation

• Patient's consent, their next of kin consent, or emergency inclusion

Non inclusion criteria :

• Chronic long-term antiepileptic treatment upon admission or patient with uncontrolled seizures
• Chronic or progressive central neurological pathologies of traumatic, inflammatory, vascular, infectious, neoplastic, or degenerative origin, defined by cognitive impairments preventing independent living or an IQCODE score > 4.5
• Patient with moderate to severe dementia
• Patient with psychiatric history and/or suicide attempts
• Severe head trauma within the past 3 months
• Patients with limitations on active therapies or for whom therapeutic commitment is not maximal
• Patient presenting a prolonged QTc interval on ECG and/or at risk of cardiovascular disease
• Concomitant treatment with Methotrexate during the administration of the investigational treatment
• Allergy to levetiracetam
• Minor patients
• Ongoing pregnancy (blood or urinary βHCG)
• Breastfeeding women
• Patients under guardianship or trusteeship
• Non-affiliation with social security or CMU
• Participation in another interventional trial with a drug that may interact with levetiracetam or may impact the evaluation of KiSS trial outcomes. In case of doubt, please contact the trial's coordinating investigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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280 participants in 2 patient groups, including a placebo group

Early Levetiracetam administration

Experimental group

Treatment:

Drug: Levetiracetam IV

Placebo control

Placebo Comparator group

Treatment:

Other: Placebo control