Clinical trial NCT01386840: IndiaCLEN Multicentre Trial of Home Versus Hospital Oral Amoxicillin for Management of Severe Pneumonia in Children
Official title: IndiaCLEN Multicentric Trial of Home Versus Hospital Oral Amoxicillin for Management of Severe Pneumonia in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pneumonia
Keywords: Efficacy of Treatment
Severe
home treatment
treatment at hospital
Lead sponsor: Lata Medical Research Foundation, Nagpur
Sponsor class: OTHER
Collaborators: name: Indira Gandhi Medical College, Shimla
name: International Clinical Epidemiology Network (INCLEN) TRUST
name: MCH-STAR Initiative, India
First posted: 2011-07-01
Enrollment: 1118
Sex: ALL
Minimum age (years): 3
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and efficacy of oral amoxicillin in treating WHO defined severe pneumonia(cough and fast breathing with lower chest indrawing) at home and at hospital using an open labelled multicentric prospective two-arm randomized clinical trial to determine the differences in failure of treatment with a 7 day course of oral amoxicillin administered for first 48 hours in the hospital in comparison to being sent home after enrolment, in children 3 to 59 months old who have severe pneumonia. The investigators developmental hypothesis were to test whether the community/home based oral amoxicillin is efficacious for treating severe pneumonia.

Detailed description: Primary objectives of this trial are to assess the rates of treatment failure (as defined below) within the first 7 days or efficacy of a 7 day course of oral amoxycillin when administered at home in comparison to administration of oral amoxycillin for first 48 hours in the hospital.

Treatment failure is defined as follows-

* Clinical deterioration of disease any time after enrollment: developing any sign of very severe disease such as persistent vomiting (vomiting repeated thrice within an hour due to any reason), central cyanosis, grunt, stridor, abnormally sleepy or difficult to wake, inability to drink, convulsions, or death.
* Change of antibiotic: due to persistent vomiting (vomiting of amoxycillin within 20 minutes of administration; 3 such attempts), or, developing a co-morbid condition, or persisting fever \> 98.6°F with lower chest indrawing even after 3rd day, or, fever alone at or after day 5, or, lower chest indrawing alone (non responsive to three doses of nebulization with bronchodilator) at or after day 5(as reported by the mother), or, persistence of fast breathing after day 7 which is non responsive to three doses of nebulisation with bronchodilator.
* Hospitalization: any time in home managed patients or clinical decision to extend the hospitalization longer than 48 hours in hospitalized children or re-hospitalization in those discharged after 48 hours from hospital. It could be related to pneumonia, or to therapy with amoxycillin \[relatedness determined by the Data \& Safety Monitoring Board (DSMB)\].
* Children who need to restart antibiotics i.e. "failure of treatment", between day 8th and day 14th due to reappearance of any danger signs, lower chest indrawing or fast breathing which is non responsive to three trials of nebulization with bronchodilator.
* Serious adverse event considered possibly or probably related to amoxycillin.
* Left against medical advice (LAMA) or Voluntary withdrawal of consent from study from enrollment uptill day 14th.
* Loss to follow up uptill day 14th.

Secondary objectives of this trial are to determine in children receiving oral amoxycillin for severe pneumonia, the following:

* Determine the proportion of children who need to restart antibiotics i.e. "failure of treatment", between day 8th and day 14th due to reappearance of any danger signs, lower chest indrawing or fast breathing which is non responsive to three trials of nebulization with bronchodilator.
* To identify clinical predictors at baseline and during the course of treatment that predicts "failure of oral treatment", from enrollment till day 14th.
* The costs of home and hospital management of severe pneumonia with oral amoxycillin.
* Left against medical advice (LAMA) or Voluntary withdrawal of consent from day 7th to day 14th.
* Loss to follow up from day 8th to day 14th.

Eligibility criteria: Inclusion Criteria:

* Children aged 3 to 59 months with pneumonia and lower chest wall indrawing
* Ability to take orally
* Absence of radiological consolidation or effusion
* Informed consent by a legal guardian

Exclusion Criteria:

Children with any of the following conditions:

* Very severe pneumonia/disease
* Respiratory rate \> 70/min
* Persistent vomiting
* Known prior episodes of asthma, or, three or more prior episodes of wheezing
* LCI that resolves after three doses of bronchodilator therapy1
* Documented use of prior oral antibiotics for 48 hours
* Severe malnutrition (weight for height \< 3SD or kwashiorkor)
* Known penicillin or amoxicillin allergy
* Hospitalization in the last two weeks
* Known or clinically recognizable HIV, congenital cardiac or respiratory anomalies, chronic lung disease including bronchopulmonary dysplasia, neurological impairment that affects respiratory function, renal diseases, malignant or haematological diseases.
* Other diseases requiring antibiotic therapy at presentation, such as meningitis,dysentery, osteomyelitis, septic arthritis, evident tuberculosis, etc.
* Anaemia requiring blood transfusion
* Kerosene poisoning
* Measles in the last 15 days
* Previous inclusion in the study or already included in another study
* Living outside a pre-defined area
* Parental or caretaker refusal to participate in the study

Primary outcomes:
measure: To assess the efficacy of a 7 day course of oral amoxycillin when administered at Home in comparison to administration of oral amoxycillin for first 48 hours in the hospital
timeFrame: Day of enrollment to Day 7
Secondary outcomes:
measure: To determine factors leading to treatment failure from day 8 to day 14 and costs of home and hospital management of severe pneumonia with oral amoxycillin
timeFrame: Day 8 to Day 14
Other outcomes:
Locations:
city: Nagpur
country: India
facility: Indira Gandhi Govt. Medical College, Nagpur
state: Maharashtra
city: Pune
country: India
facility: B.J. Medical College, Pune
state: Maharashtra
city: Wardha
country: India
facility: Mahatma Gandhi Institute of Medical Sciences, Sevagram
state: Maharashtra
city: Chennai
country: India
facility: Institute of Child Health, Chennai
state: Tamilnadu
city: Aligarh
country: India
facility: Jawaharlal Nehru Medical College, Aligarh Muslim University
state: Uttar Pradesh
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical Sciences, Chandigarh
Study officials:
affiliation: Professor And Head, Pediatrics, Indira Gandhi Govt. Medical College & CEO and Vice President, Lata MEdical Research Foundation, Nagpur
name: Archana B Patel, MD,DNB,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Patel AB, Bang A, Singh M, Dhande L, Chelliah LR, Malik A, Khadse S; ISPOT Study Group. A randomized controlled trial of hospital versus home based therapy with oral amoxicillin for severe pneumonia in children aged 3 - 59 months: The IndiaCLEN Severe Pneumonia Oral Therapy (ISPOT) Study. BMC Pediatr. 2015 Nov 17;15:186. doi: 10.1186/s12887-015-0510-9.