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

NCT ID: NCT06851078

Last Updated: 2025-03-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 280 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-15
• Study Completion Date: 2027-06-15

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.

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Early Levetiracetam administration

Group Type: EXPERIMENTAL

Levetiracetam IV

Intervention Type: DRUG

1000 mg twice a day during 7 days maximum

Placebo control

Group Type: PLACEBO_COMPARATOR

Placebo control

Intervention Type: OTHER

NaCl 0.9% sodium chloride in the same route and method of administration as experimental treatment

Interventions

Levetiracetam IV

1000 mg twice a day during 7 days maximum

Intervention Type: DRUG

Placebo control

NaCl 0.9% sodium chloride in the same route and method of administration as experimental treatment

Intervention Type: OTHER

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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Shidasp Siami, MD

Role: CONTACT

shidasp.siami@ch-sudessonne.fr

160807940 ext. +33

Jérôme Lambert, MD PhD

Role: CONTACT

jerome.lambert@u-paris.fr

0142499742 ext. +33

Other Identifiers

APHP200068

Identifier Type: -

Identifier Source: org_study_id