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

Phase 3Not Yet RecruitingNCT06851078

Assistance Publique - Hôpitaux de Paris280 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

280

Conditions

Septic Shock

Interventions

Levetiracetam IV

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Number of days alive without delirium or coma

Time frame: 14 days after randomization

Secondary Outcomes

Mortality in intensive care

Time frame: At day 28

Mortality in intensive care

Time frame: At day 90

Mortality in hospital

Time frame: At day 28

Mortality in hospital

Time frame: At day 90

Overall survival

Time frame: At day 90

Duration of mechanical ventilation

Time frame: At day 28

Length of stay in intensive care unit

Time frame: Up to day 90

Length of stay in hospital

Time frame: Up to day 90

Occurrence of epileptic seizures

From Day 1 to Day 14 (confirmed by EEG or tonic-clonic seizures) and/or occurrence of epileptic abnormalities (periodic epileptic discharges)

Time frame: Up to day 14

Time between cessation of sedation and awakening

Defined by spontaneous eye opening, among patients not deceased under sedation

Time frame: At day 90

Severity of cognitive impairment

Evaluated by a telephone survey using Telephone MoCA (Montreal Cognitive Assessment). The scores ranges from 0 to 30. A score of 26 or higher is typically considered normal. A score of 25 or lower may indicate cognitive impairment, such as mild cognitive impairment (MCI) or early-stage dementia.

Time frame: At day 90

Severity of anxiety and depression

Assessed with HADS (Hospital Anxiety and Depression Scale) scale Score varies from 0 to 21 for each componant (Anxiety and depression) The higher the score, the more severe the anxiety or depression.

Time frame: At day 90

Presence of post-traumatic stress (PTSD)

Assessed by IES-R (Impact of Event Scale Revisited) The total score can range from 0 to 88. Higher scores indicate greater trauma-related distress and a higher likelihood of experiencing PTSD symptoms.

Time frame: At day 90

Quality of life scoring

Using EQ-5D-5L. It evaluates five dimensions : mobility, self-care, usual activities, pain/discomfort and anxiety/depression and each dimension has five levels : no problems, slight problems, moderate problems, severe problems and extreme problems. Answers are given on a 5-point scale by domain, the higher the score, the poorer the quality of life.

Time frame: At day 90

Autonomy in daily life

Using Katz Index of Independence in Activities of Daily Living (ADL) The score varies from 0 to 6, the lower the score, the more dependent the person.

Time frame: At day 90

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

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts