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

NCT06851078 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: APHP200068
• Study Type: interventional
• Target: 280
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• Number of days alive without delirium or coma

  14 days after randomization

Secondary Outcomes (15)

• Mortality in intensive care

  At day 28

• Mortality in intensive care

  At day 90

• Mortality in hospital

  At day 28

• Mortality in hospital

  At day 90

• Overall survival

  At day 90

Study Arms (2)

Early Levetiracetam administration

EXPERIMENTAL

Drug: Levetiracetam IV

Placebo control

PLACEBO COMPARATOR

Other: Placebo control

Interventions

Levetiracetam IV DRUG

1000 mg twice a day during 7 days maximum

Early Levetiracetam administration

Placebo control OTHER

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

Placebo control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Shock, Septic

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Central Study Contacts

Shidasp Siami, MD

CONTACT

160807940; shidasp.siami@ch-sudessonne.fr

Jérôme Lambert, MD PhD

CONTACT

0142499742; jerome.lambert@u-paris.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase III, multicenter, comparative, randomized, double-blind, placebo-controlled study

Study Record Dates

• First Submitted: February 24, 2025
• First Posted: February 28, 2025
• Study Start: March 15, 2025
• Primary Completion (Estimated): June 15, 2027
• Study Completion (Estimated): June 15, 2027
• Last Updated: March 12, 2025

Record last verified: 2025-02