Clinical trial NCT02678195: 3 Days Versus 5 Days Amoxicillin for Chest-indrawing Childhood Pneumonia in Malawi
Official title: Double-blind Randomized Controlled Clinical Trial of 3 Days Versus 5 Days Amoxicillin Dispersible Tablets for Chest-indrawing Childhood Pneumonia Among Children 2-59 Months of Age Presenting to Kamuzu Central Hospital in Lilongwe, Malawi
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pneumonia
Lead sponsor: Save the Children
Sponsor class: OTHER
Collaborators: name: University of North Carolina
name: University of Washington
First posted: 2016-02-09
Enrollment: 3000
Sex: ALL
Minimum age (years): 2
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This clinical trial evaluates the duration of treatment of chest-indrawing pneumonia in children. Half the children will receive 3 days of amoxicillin dispersible tablets (DT) and then 2 days of placebo, while the other half will receive 5 days of amoxicillin DT.


Eligibility criteria: Inclusion Criteria:

* Male or female, 2 to 59 months of age.
* History of cough \<14 days or difficult breathing with chest-indrawing.
* Ability and willingness of child's caregiver to provide informed consent and to be available for follow-up for the planned duration of the study, including accepting a home visit if he/she fails to return to Kamuzu Central Hospital (KCH) for a scheduled study follow-up visit.

Exclusion Criteria:

* If chest-indrawing observed at screening resolves after bronchodilator challenge, among those with wheeze at screening.
* Severe respiratory distress (e.g., grunting, nasal flaring, head nodding, or severe chest-indrawing).
* Presence of World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) danger signs including: lethargy or unconsciousness, convulsions, vomiting everything, or inability to drink or breastfeed.
* Hypoxia (SaO2 \< 90% on room air, as assessed by a Lifebox pulse oximeter).
* Stridor when calm.
* HIV-1 seropositivity or HIV-1 exposure, assessed as follows:

  * An HIV-positive result upon rapid antibody test will exclude any child from this study.
  * If a child is less than 12 months or age with a positive rapid test result, the child will be referred to receive additional confirmatory HIV testing (e.g., dried blood spot filter paper test) and follow-up from KCH staff, as per standard of care. Even if the confirmatory HIV testing subsequently shows that child is HIV-negative, he or she will remain excluded from the study.
  * If a child is less than 24 months of age and has an HIV-negative result upon rapid antibody test, the child's biological mother's HIV status will need to be assessed. If the mother is HIV-positive, the child will be excluded. If the mother has a documented HIV-negative test result from within the past 6 weeks, the child will be included. If the mother does not have documentation of an HIV-negative test result, she will be tested via rapid antibody testing to determine the child's eligibility for this study.
  * If a child is over 24 months of age, an HIV-negative rapid antibody test is required for inclusion in the study.
  * Note: If a child has documentation of an HIV-negative test result from within the past 6 weeks, that test result will be used for the child's eligibility assessment according to the algorithm described above.
* Severe acute malnutrition (i.e., weight for height/length \< -3 SD, mid-upper arm circumference \<115 mm, or edema).
* Possible tuberculosis (coughing for more than 14 days).
* Severe anemia, classified by WHO pocketbook guidelines (i.e., severe palmar pallor or hemoglobin \<8.0 g/dL)
* Severe malaria, classified by WHO pocketbook guidelines (e.g., positive malaria rapid diagnostic test (mRDT) with any danger sign, stiff neck, abnormal bleeding, clinical jaundice, or hemoglobinuria)
* Known allergy to penicillin or amoxicillin.
* Receipt of an antibiotic treatment in the 48 hours prior to the study based on caregiver's self-report and/or documentation in child's medical record.
* Hospitalized within 14 days prior to the study.
* Living outside Lilongwe urban area, the study catchment area.
* Any medical or psychosocial condition or circumstance that, in the opinion of the investigators, would interfere with the conduct of the study or for which study participation might jeopardize the child's health.
* Any non-pneumonia acute medical illness which requires antibiotic treatment per local standard of care.
* Participation in a clinical study of another investigational product within 12 weeks prior to randomization or planning to begin participation during this study.
* Prior participation in an Innovative Treatments in Pneumonia (ITIP) study during a previous pneumonia diagnosis.

Primary outcomes:
measure: Proportion of children failing treatment
timeFrame: 6 days
Secondary outcomes:
Other outcomes:
Locations:
city: Lilongwe
country: Malawi
facility: Bwaila District Hospital
city: Lilongwe
country: Malawi
facility: Kamuzu Central Hospital
Study officials:
affiliation: Save the Children
name: Amy Ginsburg, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ginsburg AS, May S. Analysis of serious adverse events in a pediatric community-acquired pneumonia randomized clinical trial in Malawi. Sci Rep. 2022 Mar 3;12(1):3538. doi: 10.1038/s41598-022-07582-w.
citation: Mvalo T, McCollum ED, Fitzgerald E, Kamthunzi P, Schmicker RH, May S, Phiri M, Chirombo C, Phiri A, Ginsburg AS. Chest radiography in children aged 2-59 months enrolled in the Innovative Treatments in Pneumonia (ITIP) project in Lilongwe Malawi: a secondary analysis. BMC Pediatr. 2022 Jan 10;22(1):31. doi: 10.1186/s12887-021-03091-3.
citation: Ginsburg AS, Mvalo T, Nkwopara E, McCollum ED, Phiri M, Schmicker R, Hwang J, Ndamala CB, Phiri A, Lufesi N, May S. Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children. N Engl J Med. 2020 Jul 2;383(1):13-23. doi: 10.1056/NEJMoa1912400.
citation: Ginsburg AS, May SJ, Nkwopara E, Ambler G, McCollum ED, Mvalo T, Phiri A, Lufesi N, Sadruddin S. Methods for conducting a double-blind randomized controlled clinical trial of three days versus five days of amoxicillin dispersible tablets for chest indrawing childhood pneumonia among children two to 59 months of age in Lilongwe, Malawi: a study protocol. BMC Infect Dis. 2018 Sep 21;18(1):476. doi: 10.1186/s12879-018-3379-z.