NCT02760420

Brief Summary

The purpose of this study to assess the effectiveness of no antibiotic treatment for fast breathing, community-acquired childhood pneumonia in a malaria-endemic region of Malawi.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,126

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Jun 2016

Typical duration for phase_4

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 1, 2016

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 3, 2016

Completed
29 days until next milestone

Study Start

First participant enrolled

June 1, 2016

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2019

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2019

Completed
Last Updated

February 18, 2021

Status Verified

February 1, 2021

Enrollment Period

2.7 years

First QC Date

May 1, 2016

Last Update Submit

February 17, 2021

Conditions

Pneumonia

Outcome Measures

Primary Outcomes (1)

  • Proportion of children failing treatment

    4 days

Study Arms (2)

Placebo

EXPERIMENTAL

250 mg of placebo (dispersible tablet) DT in two divided doses based on age bands (500 mg/day for children 2 months up to 12 months, 1000 mg/day for children 12 months up to 3 years, and 1,500 mg/day for children 3 years up to 5 years of age)

Drug: Placebo

3 Days

ACTIVE COMPARATOR

250 mg amoxicillin (dispersible tablet) DT in two divided doses based on age bands (500 mg/day for children 2 months up to 12 months, 1000 mg/day for children 12 months up to 3 years, and 1,500 mg/day for children 3 years up to 5 years of age)

Drug: Amoxicillin

Interventions

AmoxicillinDRUG

Oral amoxicillin dispersible tablets (DT), 250 mg tablets, given according to age band, two times daily

3 Days
PlaceboDRUG

Oral placebo dispersible tablets (DT), 250 mg tablets, given according to age band, two times daily

Placebo

Eligibility Criteria

Age2 Months - 59 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • History of cough \<14 days or difficult breathing with fast breathing (for children 2 to \<12 months of age, \>50 breaths/minute and for children \>12 months of age, \> 40 breaths/minute).
  • Ability and willingness of children'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) with the child for a scheduled study follow-up visit.

You may not qualify if:

  • If fast breathing observed at screening resolves after bronchodilator challenge.
  • Chest-indrawing.
  • Severe respiratory distress, classified by World Health Organization (WHO) pocketbook guidelines (e.g., grunting, nasal flaring, head nodding, crackles on auscultation, or very severe chest-indrawing).
  • Presence of WHO Intergrated 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 or breastfeeding 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 12 months of age or breastfeeding 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 3 months, 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.
  • Note: If a child has documentation of an HIV-negative test result from within the past 3 months, that test result will be used for the child's eligibility assessment.
  • Severe acute malnutrition (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 (i.e., positive mRDT with any danger sign, stiff neck, abnormal bleeding, clinical jaundice, or hemoglobinuria).
  • Known allergy to penicillin or amoxicillin.
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Bwaila District Hospital

Lilongwe, Malawi

Location

Kamuzu Central Hospital

Lilongwe, Malawi

Location

Related Publications (4)

  • 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.

    PMID: 35012490DERIVED

  • May S, Brown SP, Schmicker RH, Emerson SS, Nkwopara E, Ginsburg AS. Non-inferiority designs comparing placebo to a proven therapy for childhood pneumonia in low-resource settings. Clin Trials. 2020 Apr;17(2):129-137. doi: 10.1177/1740774519888460. Epub 2019 Dec 8.

    PMID: 31814441DERIVED

  • Nkwopara E, Schmicker R, Mvalo T, Phiri M, Phiri A, Couasnon M, McCollum ED, Ginsburg AS. Analysis of serious adverse events in a paediatric fast breathing pneumonia clinical trial in Malawi. BMJ Open Respir Res. 2019 Sep 3;6(1):e000415. doi: 10.1136/bmjresp-2019-000415. eCollection 2019.

    PMID: 31548894DERIVED

  • Ginsburg AS, Mvalo T, Nkwopara E, McCollum ED, Ndamala CB, Schmicker R, Phiri A, Lufesi N, Izadnegahdar R, May S. Placebo vs Amoxicillin for Nonsevere Fast-Breathing Pneumonia in Malawian Children Aged 2 to 59 Months: A Double-blind, Randomized Clinical Noninferiority Trial. JAMA Pediatr. 2019 Jan 1;173(1):21-28. doi: 10.1001/jamapediatrics.2018.3407.

    PMID: 30419120DERIVED

MeSH Terms

Conditions

Pneumonia

Interventions

Amoxicillin

Condition Hierarchy (Ancestors)

Respiratory Tract InfectionsInfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

AmpicillinPenicillin GPenicillinsbeta-LactamsLactamsAmidesOrganic ChemicalsSulfur CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Amy Ginsburg, MD, MPH

    Consultant, University of Washington

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 1, 2016

First Posted

May 3, 2016

Study Start

June 1, 2016

Primary Completion

March 1, 2019

Study Completion

June 1, 2019

Last Updated

February 18, 2021

Record last verified: 2021-02

Locations

MA(2)