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

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.

Study Overview

• Status: Terminated
• Conditions: Seizures; Pneumococcal Meningitis
• Intervention / Treatment: Drug: Phenytoin; Drug: placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: M. Carmen Cabellos, MD; Phone Number: +34932607625; Email: ccabellos@bellvitgehospital.cat

Study Locations

• Spain
  • A Coruña, Spain, 15006
    • Hospital Juan Canalejo
  • Barcelona, Spain, 08025
    • Fundacio Institut per la Recerca de l'hospital de la Santa Creu i Sant Pau
  • Sevilla, Spain, 41013
    • Hospital Virgen del Rocío
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: phenytoin prophylaxis; 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; 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.
Placebo Comparator: placebo; placebo vials and pills labeled as phenytoin prophylaxis vials and pills	Drug: placebo; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: M. Carmen Cabellos Minguez
• Collaborators: Hospital Clinic of Barcelona; Germans Trias i Pujol Hospital; Hospital Universitario Ramon y Cajal; Hospital Universitario Virgen Macarena; Hospital Universitari de Bellvitge; Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau; Hospital Mutua de Terrassa; Hospitales Universitarios Virgen del Rocío; Hospital Universitario La Paz; Hospital Vall d'Hebron; Hospital Juan Canalejo
• Investigators: Principal Investigator: M. Carmen Cabellos, MD, Hospital Universitari de Bellvitge

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2011
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: November 21, 2011
• First Submitted That Met QC Criteria: November 22, 2011
• First Posted (Estimate): November 23, 2011

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Placebo-controlled; Randomized; Double blind; Phenytoin prophylaxis; Pneumococcal meningitis; Patient 50 years or older
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Neurologic Manifestations; Central Nervous System Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Pneumococcal Infections; Seizures; Meningitis; Meningitis, Pneumococcal; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Phenytoin
• Other Study ID Numbers: INFSNC1