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Comparison of 5 versus 10 days of ceftriaxone therapy for bacterial meningitis in children: multicentre study in Bangladesh, Malawi, Pakistan, South Africa, Vietnam and Egypt
ISRCTN ISRCTN38717320
DOI 10.1186/ISRCTN38717320
ClinicalTrials.gov identifier
EudraCT number
Public title Comparison of 5 versus 10 days of ceftriaxone therapy for bacterial meningitis in children: multicentre study in Bangladesh, Malawi, Pakistan, South Africa, Vietnam and Egypt
Scientific title
Acronym N/A
Serial number at source WHO/CAH ID 98011
Study hypothesis Primary objective:
To determine if the bacteriologic failure* between 6 - 40 days is equivalent (after randomising the day 5 survivors) between 10 days versus 5 days of ceftriaxone therapy for treatment of acute bacterial meningitis in children aged 2 months up to 12 years.

Secondary objectives:
1. In children who receive 5 versus 10 days of ceftriaxone therapy for acute bacterial meningitis following rates will be compared by day 40 (after admission):
1.1. Mortality rates by day 40
1.2. Hearing loss on day 40
1.3. Blindness on day 40
1.4. Neurologic, motor deficits by day 40
1.5. Treatment failure
1.6. Bacterial pathogens
2. In children who receive 5 versus 10 days of ceftriaxone therapy for acute bacterial meningitis we will compare the rates of the following at 190 + 30 days after admission:
2.1. Mortality rates
2.2. Hearing loss
2.3. Blindness
2.4. Neurologic, motor and developmental deficits

*Bacteriologic failure will be reappearance of bacteria in CSF between 6-40 days

Please note that after discussions with the Data Safety Monitoring Board (DSMB), the following was decided:
1. In the DSMB meeting in 2002, in order to improve enrolment, the age of enrolment was increased to 144 months. Therefore, the upper limit of weight was also increased from 18.5 kg (see changes made to inclusion criteria)
2. In the DSMB meeting in 2006, due to the challenge in enrolling 1500 children (the original target number of participants, the DSMB decided to stop enrolment after reviewing the interim analysis data. They felt that continuing the trial to achieve the sample size to that originally planned is unlikely to alter in an important way the findings, or the recommendations based on those findings.
Lay summary Not provided at time of registration
Ethics approval Ethics approval received from the Institutional Review Board (IRB) of:
1. Dhaka Shishu Hospital, Institute of Child Health, Dhaka, Bangladesh
2. Abbasiyya Fever Hospital, Cairo, Egypt
3. College of Medicine, Blantyre, Malawi
4. Pakistan Institute of Medical Sciences, Islamabad, Pakistan
5. Aga Khan University, Karachi, Pakistan
6. Children Hospital No 1, Ho Chi Minh City, Vietnam
7. University of Natal, Durban
8. World Health Organization (WHO) Ethical Review Committee
Study design Randomised controlled trial
Countries of recruitment Bangladesh, Egypt, Malawi, Pakistan, South Africa, Viet Nam
Disease/condition/study domain Bacterial meningitis
Participants - inclusion criteria 1. Aged 2 - 71 months (as of 11/10/07 the upper age limit was increased to 144 months)
2. Weight 3.0 kg - 18.5 kg (as of 11/10/07 the upper weight limit was increased)
3. Children of acute bacterial meningitis with positive Cerebrospinal Fluid (CSF) culture or latex for H. influenzae, St. pneumoniae, N. meningitidis
4. If CSF culture negative, then CSF White Blood Cell count (WBC) greater than 10/ml and blood culture positive by day 3
5. Treatment with injectable ceftriaxone since admission
6. Informed consent from parent/guardian
Participants - exclusion criteria 1. Neurological conditions
2. Known cerebral palsy, immunodeficiency or chronic afebrile seizure disorder
3. Progressive brain degenerative disorder
4. Cranial fracture with or without CSF leak
5. Known cyanotic heart disorder
6. Known deafness prior to admission
7. Evidence of measles, mumps or chicken pox present
8. Child randomised to the study before
9. Illness more than 7 days
10. Allergic to cephalosporins
11. Lives outside follow-up area of study
Anticipated start date 01/09/2002
Anticipated end date 14/06/2006
Status of trial Completed
Patient information material
Target number of participants 1500 (787 recruited as of end of trial)
Interventions All children to receive ceftriaxone once daily for 1 - 5 days.
From 6 - 10 days children will be randomised to receive the same dose of ceftriaxone or placebo.
Primary outcome measure(s) Rate of bacteriologic failure defined as:
1. Cerebrospinal Fluid (CSF) or blood culture positive* on day 6 to 40 for original organism, or
2. CSF or blood culture positive on days 6 to 40 in a patient who had culture negative bacterial meningitis

Note: Repeat lumber puncture will be done between 48-72 hours of admission. A repeat blood cultures will only be done if condition of the patient requires it.

*for H. influenzae, S. pneumoniae, N. meningitidis
Secondary outcome measure(s) 1. Perceived treatment failure
2. Hearing loss: Day 40 screen Otoacoustic Emissions (OAE), Auditory Brainstem Response (ABR) greater than 40 db
3. Blindness diagnosed at day 40
4. Motor deficit at day 40 including:
4.1. Two or more abnormalities of tone or strength in any of the limbs or neck, or
4.2. Any palsy of VI or VII cranial nerves
5. Developmental score: abnormal developmental screening on day 190 + 30 days as evaluated by Denver Screening method
6. Seizures: any seizure without fever presenting on days 10 to 40 or 41 to 190 + 30 days
7. Hydrocephalus: defined as any patient with ventriculo-peritoneal shunting or clinical signs and head circumference measurements consistent with hydrocephalous and the perceived need of ventricular derivation
8. Death of an enrolled patient by any cause between days 6 - 40
9. Death of an enrolled patient by any cause between 41 - 190 days
10. Bacterial pathogen
Sources of funding The Department of Child and Adolescent Health (CAH)/World Health Organization (WHO) (Switzerland)
Trial website
Publications 1. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21620467
Contact name Dr  Shamim  Qazi
  Address 20, Avenue Appia
  City/town Geneva -27
  Zip/Postcode CH 1211
  Country Switzerland
  Email qazis@who.int
Sponsor The Department of Child and Adolescent Health (CAH)/World Health Organization (WHO) (Switzerland)
  Address 20, Avenue Appia
  City/town Geneva -27
  Zip/Postcode CH 1211
  Country Switzerland
  Sponsor website: http://www.who.int
Date applied 27/07/2004
Last edited 25/08/2011
Date ISRCTN assigned 28/07/2004
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