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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Hospital Universitari de Bellvitge
Sponsor:
Collaborators:
Hospital Universitari de Bellvitge
Hospital Vall d'Hebron
Germans Trias i Pujol Hospital
Hospital Clinic of Barcelona
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Hospitales Universitarios Virgen del Rocío
Hospital Universitario La Paz
Hospital Universitario Ramon y Cajal
Hospital Juan Canalejo
Hospital Mutua de Terrassa
Hospital Virgen Macarena
Information provided by (Responsible Party):
M. Carmen Cabellos Minguez, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier:
NCT01478035
First received: November 21, 2011
Last updated: December 19, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Seizures
Pneumococcal Meningitis
Drug: Phenytoin
Drug: placebo
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Hospital Universitari de Bellvitge:

Primary Outcome Measures:
  • Presence of seizures (clinical) after initiation of phenytoin /placebo prophylaxis during the 10 days of antibiotic therapy [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    Presence of seizures (clinical) after initiation of phenytoin /placebo prophylaxis during the 10 days of antibiotic therapy


Secondary Outcome Measures:
  • Need for anticonvulsivant therapy at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Need for anticonvulsivant therapy at 3 months


Estimated Enrollment: 122
Study Start Date: November 2011
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01478035

Contacts
Contact: M. Carmen Cabellos, MD +34932607625 ccabellos@bellvitgehospital.cat

Locations
Spain
Hospital Universitari de Bellvitge Recruiting
L'Hospitalet de Llobregat, Barcelona, Spain, 08907
Contact: Carmen Cabellos    34932607625    ccabellos@bellvitgehospital.cat   
Principal Investigator: M. Carmen Cabellos, MD         
Hospital Juan Canalejo Recruiting
A Coruña, Spain, 15006
Contact: Efren Sanchez       Efren.Sanchez.Vidal@sergas.es   
Principal Investigator: Efren Sanchez         
Fundacio Institut per la Recerca de l'hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain, 08025
Contact: Virginia Pomar       VPomar@santpau.cat   
Principal Investigator: Virginia Pomar         
Hospital Virgen del Rocio Recruiting
Sevilla, Spain, 41013
Contact: Enrique Mejias       MEJ-MEJIAS@telefonica.net   
Principal Investigator: Enrique Mejias         
Sponsors and Collaborators
M. Carmen Cabellos Minguez
Hospital Universitari de Bellvitge
Hospital Vall d'Hebron
Germans Trias i Pujol Hospital
Hospital Clinic of Barcelona
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Hospitales Universitarios Virgen del Rocío
Hospital Universitario La Paz
Hospital Universitario Ramon y Cajal
Hospital Juan Canalejo
Hospital Mutua de Terrassa
Hospital Virgen Macarena
Investigators
Principal Investigator: M. Carmen Cabellos, MD Hospital Universitari de Bellvitge
  More Information

No publications provided

Responsible Party: M. Carmen Cabellos Minguez, Medical Doctor, Hospital Universitari de Bellvitge
ClinicalTrials.gov Identifier: NCT01478035     History of Changes
Other Study ID Numbers: INFSNC1
Study First Received: November 21, 2011
Last Updated: December 19, 2012
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Hospital Universitari de Bellvitge:
Phenytoin prophylaxis
Pneumococcal meningitis
Randomized
Placebo-controlled
Double blind
Patient 50 years or older

Additional relevant MeSH terms:
Meningitis
Meningitis, Pneumococcal
Meningitis, Bacterial
Seizures
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Central Nervous System Infections
Central Nervous System Bacterial Infections
Bacterial Infections
Pneumococcal Infections
Streptococcal Infections
Gram-Positive Bacterial Infections
Phenytoin
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 22, 2014