Clinical trial NCT01478035: Study on the Efficacy of Phenytoin in the Prophylaxis of Seizures of Patients With Pneumococcal Meningitis at Least 50 Yrs Old.
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Seizures
Pneumococcal Meningitis
Keywords: Phenytoin prophylaxis
Pneumococcal meningitis
Randomized
Placebo-controlled
Double blind
Patient 50 years or older
Lead sponsor: Hospital Universitari de Bellvitge
Sponsor class: OTHER
Collaborators: name: Hospital Universitari de Bellvitge
name: Hospital Vall d'Hebron
name: Germans Trias i Pujol Hospital
name: Hospital Clinic of Barcelona
name: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Hospitales Universitarios Virgen del Rocío
name: Hospital Universitario La Paz
name: Hospital Universitario Ramon y Cajal
name: Hospital Juan Canalejo
name: Hospital Mutua de Terrassa
name: Hospital Universitario Virgen Macarena
First posted: 2011-11-23
Enrollment: 26
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
measure: Presence of seizures (clinical) after initiation of phenytoin /placebo prophylaxis during the 10 days of antibiotic therapy
timeFrame: 10 days
Secondary outcomes:
measure: Need for anticonvulsivant therapy at 3 months
timeFrame: 3 months
Other outcomes:
Locations:
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: A Coruña
country: Spain
facility: Hospital Juan Canalejo
city: Barcelona
country: Spain
facility: Fundacio Institut per la Recerca de l'hospital de la Santa Creu i Sant Pau
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
Study officials:
affiliation: Hospital Universitari de Bellvitge
name: M. Carmen Cabellos, MD
role: PRINCIPAL_INVESTIGATOR
References: