Multicentre randomised clinical study to compare the efficacy of chloramphenicol with that of ampicillin plus gentamicin in children aged 2 to 59 months with very severe pneumonia: multicentre study conducted in Bangladesh, India, Mexico, Pakistan, Yemen, Vietnam, and Zambia

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN39543942
• Date of registration: 28/07/2004
• Prospective Registration: No
• Primary sponsor: The Department of Child and Adolescent Health (CAH)/World Health Organization (WHO) (Switzerland)
• Public title: Multicentre randomised clinical study to compare the efficacy of chloramphenicol with that of ampicillin plus gentamicin in children aged 2 to 59 months with very severe pneumonia: multicentre study conducted in Bangladesh, India, Mexico, Pakistan, Yemen, Vietnam, and Zambia
• Date of first enrolment: 01/10/2000
• Target sample size: 1182
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN39543942
• Study type: Interventional
• Study design: Randomised controlled trial (Treatment)

Countries of recruitment

Bangladesh, Ecuador, India, Mexico, Pakistan, Viet Nam, Yemen, Zambia

Contacts

• Name: Shamim Qazi

Key inclusion & exclusion criteria

Inclusion criteria: 1. Age 5 - 59 months
2. History of cough or difficult breathing
3. Central cyanosis or inability to drink
4. Caretaker is willing to sign informed consent form
Exclusion criteria: 1. Current illness greater than 10 days old
2. Past history of more than two wheezing episodes or diagnosed asthma
3. Known cardiac patient
4. Known Human Immunodeficiency Virus (HIV) infected
5. Known family member to be HIV infected
6. More than 24 hours hospitalisation within the last 7 days
7. History of severe adverse reaction to study drugs
8. Prior enrolment in the study
9. Injection of antibiotic more than 24 hours prior to enrolment
10. Stridor
11. Known renal failure or not passed urine in last 24 hours
12. Cerebral malaria
13. Bacterial meningitis
14. Clinical jaundice
15. Oral thrush
16. Hepatosplenomegaly
17. Follow-up to home not possible

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Severe pneumonia
Respiratory
Influenza and pneumonia

Intervention(s)

For the primary end-point, a total of two looks at the data would require 1,182 patients (591 in each group) to be studied. This sample size assumes a study power of 80% to look for differences between the groups, and maintains an overall two-sided alpha level of 0.05 and includes adjustment for 2% loss to follow-up.

Patients will be radomised to:
Group 1: 5 days of injectable chloramphenicol in hospital followed by 5 days of oral chloramphenicol at home
Group 2: 5 days of injectable ampicillin and gentamicin in hospital followed by 5 days of oral ampicillin and gentamicin at home

Primary Outcome(s)

The primary outcome variable is "treatment failure at day 6" defined as follows:
1. If at any time after randomisation the following occur:
1.1. Death
1.2. Development of bacterial meningitis, empyema, septic shock or renal failure
1.3. Serious adverse events leading to change of therapy or any modification of antibiotic therapy before day 6 (modification of the dosage of the antibiotic will not be considered as a "treatment failure")
1.4. Left Against Medical Advice (LAMA), or withdrawal of consent (reason of including this in treatment failure is because parents may LAMA or withdraw the consent thinking their child is not improving on the study treatment), or loss to follow-up

OR

2. Development of any of the two signs at 48 hours after randomisation:
2.1. Worsening of tachypnoea (defined as 20 breaths above baseline), or
2.2. Development/persistence of abnormal sleepiness or difficulty in awakening, or
2.3. Development/persistence of inability to drink

OR

3. Development of two or more of the following at Day 6 after randomisation:
3.1. Worsening of tachypnoea (defined as 20 breaths above baseline, or
3.2. Development/persistence of abnormal sleepiness or difficulty in awakening, or
3.3. Development/persistence of inability to drink

Secondary Outcome(s)

1. Treatment failures, as defined above, 48 hours after randomisation
2. Treatment failures, as defined above, 11 days after randomisation
3. Treatment failures, as defined above, 21 - 30 days after randomisation (if a patient develops signs given for treatment failure within two weeks after stopping treatment it will be considered a relapse)
4. Deaths by 21 ? 30 days after randomisation
5. Bacterial pathogens isolated in blood cultures from children with very severe pneumonia
6. Antimicrobial susceptibility in blood culture isolates from children with very severe pneumonia

Secondary ID(s)

WHO/CAH ID 98022

Source(s) of Monetary Support

The Department of Child and Adolescent Health (CAH)/World Health Organization (WHO) (Switzerland)