Multicentre prospective randomised clinical trial to compare the safety and efficacy of outpatient treatment with oral amoxicillin with that of injectable ampicillin in children aged 3 to 59 months: APPIS II Randomised Controlled Trial (RCT), Pakistan

ISRCTN	ISRCTN95821329
DOI	https://doi.org/10.1186/ISRCTN95821329
ClinicalTrials.gov (NCT)	NCT00227331
Protocol serial number	RPC116
Sponsor	The Department of Child and Adolescent Health (CAH)/World Health Organization (WHO) (Switzerland)
Funders	The Department of Child and Adolescent Health (CAH)/World Health Organization (WHO) (Switzerland), US Agency for International Development (USAID) (USA)

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Dr Shamim Ahmad Qazi
Scientific

World Health Organization
20 Avenue Appia
Geneva-27
CH 1211
Switzerland

Phone	+41 (0)22 791 4853
Email	qazis@who.in

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	APPIS II
Study objectives	The proportion of children aged 3 to 59 months with World Health Organization (WHO) defined severe pneumonia who fail treatment in the oral amoxicillin group will not be greater than the proportion of those who fail in the parenteral ampicillin group.
Ethics approval(s)	Approval received from: 1. Local ethics board on the 2nd December 2004 2. WHO Ethics Research Committee (ERC) on the 23rd March 2005
Health condition(s) or problem(s) studied	World Health Organization (WHO) defined severe pneumonia
Intervention	1. Parenteral Ampicillin for 2 days then sent home on oral amoxicillin for 3 days 2. Oral Amoxicillin for 5 days
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Amoxicillin, ampicillin
Primary outcome measure(s)	1. Clinical deterioration occurring any time after enrolment 2. Inability to take oral medication due to persisting vomiting as assessed by study physician 3. Change or addition of antibiotics
Key secondary outcome measure(s)	1. Treatment failure between day 6 and 14 2. Clinical deterioration (development of danger signs) between day 6 and 14 3. Development of lower chest indrawing or fast breathing, which is non responsive to three trials of nebulisation with bronchodilator between day 6 and 14
Completion date	31/08/2008

Participant type(s)	Patient
Age group	Child
Lower age limit	3 Months
Upper age limit	59 Months
Sex	All
Target sample size at registration	2100
Key inclusion criteria	1. Children aged 3 to 59 months with severe pneumonia. Severe pneumonia is defined as Lower Chest Indrawing (LCI) in children with cough and/or difficult breathing, who are able to drink and do not have central cyanosis, regardless of the respiratory rate 2. Known Human Immunodeficiency Virus (HIV) infected patients in clinical category N or A (Centers for Disease Control [CDC]) will be included 3. Informed consent by a legal guardian
Key exclusion criteria	Children with any of the following conditions will be excluded: 1. Very severe pneumonia/disease 2. Known prior episodes of asthma or three or more prior episodes of wheezing 3. LCI that resolves after three doses of bronchodilator therapy 4. Severe malnutrition (visible severe wasting or oedema) 5. Known anaphylactic reaction to penicillin or amoxicillin 6. Hospitalisation in the last two weeks 7. Other diseases requiring antibiotic therapy at presentation, such as meningitis, dysentery, osteomyelitis, septic arthritis, evident tuberculosis etc. 8. Persistent vomiting 9. Previous inclusion in the study 10. Living outside a pre-defined area 11. Parental or caretaker refusal to participate in the study
Date of first enrolment	24/02/2005
Date of final enrolment	31/08/2008

World Health Organization

Geneva-27
CH 1211
Switzerland

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	Results	05/01/2008		Yes	No