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 | https://doi.org/10.1186/ISRCTN38717320 |
| Secondary identifying numbers | WHO/CAH ID 98011 |
- Submission date
- 27/07/2004
- Registration date
- 28/07/2004
- Last edited
- 25/08/2011
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Shamim Qazi
Scientific
Scientific
20, Avenue Appia
Geneva -27
CH 1211
Switzerland
| qazis@who.int |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | |
| Study objectives | 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. |
| Ethics approval(s) | 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 |
| Health condition(s) or problem(s) studied | Bacterial meningitis |
| Intervention | 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. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Ceftriaxone |
| Primary outcome measure | 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 measures | 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 |
| Overall study start date | 01/09/2002 |
| Completion date | 14/06/2006 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 2 Months |
| Upper age limit | 71 Months |
| Sex | Both |
| Target number of participants | 1500 (787 recruited as of end of trial) |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/09/2002 |
| Date of final enrolment | 14/06/2006 |
Locations
Countries of recruitment
- Bangladesh
- Egypt
- Malawi
- Pakistan
- South Africa
- Switzerland
- Viet Nam
Study participating centre
20, Avenue Appia
Geneva -27
CH 1211
Switzerland
CH 1211
Switzerland
Sponsor information
The Department of Child and Adolescent Health (CAH)/World Health Organization (WHO) (Switzerland)
Research organisation
Research organisation
20, Avenue Appia
Geneva -27
CH 1211
Switzerland
| Website | http://www.who.int |
|---|---|
"ROR" |
https://ror.org/01f80g185 |
Funders
Funder type
Research organisation
The Department of Child and Adolescent Health (CAH)/World Health Organization (WHO) (Switzerland)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 28/05/2011 | Yes | No |
