Study on the Efficacy of Phenytoin in the Prophylaxis of Seizures of Patients With Pneumococcal Meningitis at Least 50 Yrs Old.

Condition(s) targeted: Seizures; Pneumococcal Meningitis

Intervention: Phenytoin (Drug); placebo (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: M. Carmen Cabellos Minguez

Official(s) and/or principal investigator(s):
M. Carmen Cabellos, MD, Principal Investigator, Affiliation: Hospital Universitari de Bellvitge

Overall contact:
M. Carmen Cabellos, MD, Phone: +34932607625, Email: ccabellos@bellvitgehospital.cat

To evaluate the efficacy of the prophylaxis with phenytoin in the prevention of seizures in patients with pneumococcal meningitis. Hypothesis: Administration of prophylactic phenytoin will reduce the incidence of seizures in patients with pneumococcal meningitis older than 50 yrs.

Official title: Efficacy of Phenytoin in the Prophylaxis of Seizures of Patients With Pneumococcal Meningitis at Least 50 Yrs Old. A Multi-center Comparative Randomized Double-blind and Placebo-controlled Clinical Trial

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome: Presence of seizures (clinical) after initiation of phenytoin /placebo prophylaxis during the 10 days of antibiotic therapy

Secondary outcome: Need for anticonvulsivant therapy at 3 months

Detailed description: Background: Bacterial meningitis has still a high morbi-mortality despite the global improvement in therapy.

Among complications, the presence of seizures may contribute to increase the morbi-mortality. Prophylactic phenytoin is used in clinical practice in high risk patients but this use is variable because there are not controlled clinical trials demonstrating efficacy along with antibiotics and corticosteorids. Pneumococcal episodes are associated to a higher number of seizures and a higher mortality especially in elderly patients.

Objectives: To evaluate the efficacy of the prophylaxis with phenytoin in the prevention of seizures in patients with pneumococcal meningitis. Hypothesis: Administration of prophylactic phenytoin will reduce the incidence of seizures in patients with pneumococcal meningitis older than 50 yrs.

Methodology: Multicentre, randomized, double blind placebo controlled clinical trial. Patients will be included mostly from hospitals from REIPI and CAIBER and randomly assigned to receive phenytoin or placebo.

Sample size has been estimated in 61 patients per group. Antibiotic therapy and ICP prophylaxis will be standardized in all centres. Phenytoin administration will be maintained during antibiotic therapy. End point will be incidence of seizures during hospital stay and overall mortality will be a secondary end-point. Followup visits at 1 and 3 month will be performed.

Minimum age: 50 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

Adult patients > or = 50 years old.

Diagnosed of pneumococcal meningitis due to clinical characteristics plus a positive CSF Gram stain and/or a detection of pneumococcal antigen or PCR

or

Suspected pneumococcal meningitis since it is an episode related to otitis, pneumonia, sinusitis or pericranial fistula or in patients with known risk factors such as myeloma or splenectomy.

Exclusion Criteria:

To have seizures prior to arrive to the hospital or the inclusion in the study.

Pregnancy or breastfeeding.

To have conduction abnormalities in ECG.

History of allergy or intolerance to phenytoin.

Patients with meningitis as a complication of neurosurgical procedures.

Epileptic patients taking usually anticonvulsivants.

Refusal by the patient or family to participate and/or to sign the informed consent.

M. Carmen Cabellos, MD, Phone: +34932607625, Email: ccabellos@bellvitgehospital.cat

Hospital Juan Canalejo, A Coruña 15006, Spain; Recruiting
Efren Sanchez, Email: Efren.Sanchez.Vidal@sergas.es
Efren Sanchez, Principal Investigator

Fundacio Institut per la Recerca de l'hospital de la Santa Creu i Sant Pau, Barcelona 08025, Spain; Recruiting
Virginia Pomar, Email: VPomar@santpau.cat
Virginia Pomar, Principal Investigator

Hospital Virgen del Rocio, Sevilla 41013, Spain; Recruiting
Enrique Mejias, Email: MEJ-MEJIAS@telefonica.net
Enrique Mejias, Principal Investigator

Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona 08907, Spain; Recruiting
Carmen Cabellos, Phone: 34932607625, Email: ccabellos@bellvitgehospital.cat
M. Carmen Cabellos, MD, Principal Investigator

Starting date: November 2011
Last updated: December 19, 2012