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

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

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01478035

Enrollment

Registered

2011-11-23

Start date

2011-11-30

Completion date

2015-12-31

Last updated

2023-03-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pneumococcal Meningitis, Seizures

Keywords

Phenytoin prophylaxis, Pneumococcal meningitis, Randomized, Placebo-controlled, Double blind, Patient 50 years or older

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.

Interventions

DRUGPhenytoin

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.

DRUGplacebo

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

50 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Need for anticonvulsivant therapy at 3 months	3 months	Need for anticonvulsivant therapy at 3 months

Countries

Spain

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026