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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Seizures, Pneumococcal Meningitis

Intervention / Treatment
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* Drug: Phenytoin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: phenytoin prophylaxis<br>Patients with suspected or proven pneumococcal meningitis are allocated to receive phenytoin prophylaxis or placebo to avoid seizures during the 10 days of antibiotic therapy starting after the antibiotic therapy | Drug: Phenytoin<br>* Phenytoin 18 mg /Kg/day iv as loading dose. 24 hours later phenytoin 6 mg/Kg/d in 3 divided doses iv shifting to oral route at the same dose when the patient is able to use oral route.<br>|
| Placebo Comparator: placebo<br>placebo vials and pills labeled as phenytoin prophylaxis vials and pills | Drug: placebo<br>* Placebo 18 mg /Kg/day iv as loading dose. 24 hours later placebo 6 mg/Kg/d in 3 divided doses iv shifting to oral route at the same dose when the patient is able to use oral route.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of seizures (clinical) after initiation of phenytoin /placebo prophylaxis during the 10 days of antibiotic therapy | Presence of seizures (clinical) after initiation of phenytoin /placebo prophylaxis during the 10 days of antibiotic therapy | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Need for anticonvulsivant therapy at 3 months | Need for anticonvulsivant therapy at 3 months | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phenytoin prophylaxis, Pneumococcal meningitis, Randomized, Placebo-controlled, Double blind, Patient 50 years or older