Clinical trial NCT06851078: Evaluation of Early Administration of Levetiracetam in the Prevention and Treatment Encephalopathy in Septic Shock: Randomized, Double-blind, Placebo-controlled Trial
Official title: Evaluation de l'Administration précoce de lévétiracétam Dans la prévention et le Traitement de l'encéphalopathie au Cours du Choc Septique : Essai randomisé, en Double Aveugle, contrôlé Par Placebo
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Septic Shock
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2025-02-28
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase III, multicenter, comparative, randomized, double-blind, placebo-controlled study
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Number of days alive without delirium or coma
timeFrame: 14 days after randomization
Secondary outcomes:
measure: Mortality in intensive care
timeFrame: At day 28
measure: Mortality in intensive care
timeFrame: At day 90
measure: Mortality in hospital
timeFrame: At day 28
measure: Mortality in hospital
timeFrame: At day 90
measure: Overall survival
timeFrame: At day 90
measure: Duration of mechanical ventilation
timeFrame: At day 28
measure: Length of stay in intensive care unit
timeFrame: Up to day 90
measure: Length of stay in hospital
timeFrame: Up to day 90
measure: Occurrence of epileptic seizures
timeFrame: Up to day 14
measure: Time between cessation of sedation and awakening
timeFrame: At day 90
measure: Severity of cognitive impairment
timeFrame: At day 90
measure: Severity of anxiety and depression
timeFrame: At day 90
measure: Presence of post-traumatic stress (PTSD)
timeFrame: At day 90
measure: Quality of life scoring
timeFrame: At day 90
measure: Autonomy in daily life
timeFrame: At day 90
Other outcomes:
Locations:
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