PneumoniaPhase 3NCT01399723

Amoxicillin Versus Benzyl Penicillin for Treatment of Children Hospitalised With Severe Pneumonia

A Phase 3 study testing Amoxicillin and Benzyl penicillin in people with Pneumonia, run by KEMRI-Wellcome Trust Collaborative Research Program at 6 sites in Kenya.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 2 to 59 months
Conditions the study is for: Pneumonia
What is being tested?: Amoxicillin and Benzyl penicillin
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 561 participants
Where: 6 sitesKenya
Study dates: Sep 2011to Sep 2013
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 59 months
All sexes
No healthy volunteers
Child

Who may be able to join

Clinical signs of WHO-defined severe pneumonia
Age 2 months to 59 months

Who cannot join

Clinical signs of WHO-defined very severe pneumonia
Clinical or laboratory diagnosis of meningitis
Clinical diagnosis of severe malnutrition (marasmus/kwashiorkor)
Clinical or laboratory diagnosis of severe anaemia requiring transfusion
HIV-exposure on rapid HIV antibody test (only observational data will be collected from these patients)
Elimination of signs of severe pneumonia in a child with wheeze after outpatient bronchodilator therapy

Show all 14Show fewer

Chronic condition that may underlie or contribute to a presentation with respiratory distress such as: known chronic renal or cardiac disease, presence of cerebral palsy predisposing child to aspiration/hypostatic pneumonia
Established bronchiectasis or congenital abnormality of the lower respiratory tract
Upper airway obstruction producing stridor
Admission from outpatient clinic specifically for treatment of TB
Referral from another inpatient facility following treatment with injectable antibiotics for more than 24 hours or because the initial regimen is considered to have failed
Documented history of >48hours treatment with oral amoxicillin
Failure to obtain informed consent
Penicillin allergy

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

Kenya6 sites

Bungoma District Hospital
Bungoma, Western
Embu Provincial General Hospital
Embu, Eastern
Kerugoya District Hospital
Kerugoya, Central
Kisumu East District Hospital
Kisumu, Nyanza
New Nyanza Provincial General Hospital
Kisumu, Nyanza
Mbagathi District Hospital
Nairobi, Nairobi County

Other trials in Kenya

About this study

Official title: Amoxicillin Versus Benzyl Penicillin for Severe Childhood Pneumonia Amongst Inpatients: An Open Label Randomised Controlled Non-inferiority Trial

This study seeks to determine whether clinical outcome following initial treatment of severe pneumonia with oral amoxicillin is as effective as the current standard benzyl penicillin. The study will also provide an estimate of the proportion of Kenyan children with severe pneumonia who fail treatment with a single antibiotic.

Read the detailed description

Case management for the treatment of childhood acute respiratory infections has been widely promoted in many developing countries for over 20 years. Despite this, pneumonia continues to claim over 1.5 million lives of children under five annually. The use of affordable, easily-administered, safe, effective treatments can potentially reduce the burden of childhood pneumonia. The WHO recommends the use of a single antibiotic for the treatment of severe pneumonia. Whereas in Asia, evidence from large randomized clinical trials has changed policy recommendations for treatment of severe pneumonia from parenteral penicillin to oral amoxicillin, there is little evidence to inform a similar move in African children where pneumonia is associated with poorer outcomes. In this study the investigators will investigate effectiveness of oral amoxicillin versus the current standard treatment, benzyl penicillin in severe childhood pneumonia using a randomized controlled non-inferiority design preceded by a pilot pre-intervention phase. The investigators will also collect observational data HIV-exposed / infected children with severe pneumonia. 594 children aged 2 - 59 months admitted with clinical signs of severe pneumonia to up to 7 hospitals in Kenya will be randomly assigned to receive either oral amoxicillin or injectable benzyl penicillin. They will then be followed up for the primary outcome of pre-defined treatment failure at 48 hours. The results of this trial will provide valuable data on the effectiveness of oral amoxicillin in the treatment of severe pneumonia in a population of Kenyan children and determine the practicability of conducting large pragmatic trials on pneumonia in Africa similar to those done in Asia.

Conditions: Pneumonia
Being tested: Amoxicillin, Benzyl penicillin
Keywords: Severe pneumonia
Medical subject headings: Pneumonia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AmoxicillinDrug
Oral 45mg/kg 12 hourly
Benzyl penicillinDrug
Intravenous 50,000IU/kg 6 hourly

Study groups in NCT01399723
Study group	Role	What they receive
Amoxicillin 45mg/kg 12 hourly	Experimental	Not described Receives: Drug: Amoxicillin
Benzyl Penicillin 50,000IU/kg 6 hourly	Active comparator	Not described Receives: Drug: Benzyl penicillin

What is being measured

The primary outcome is the main question the study is designed to answer.

Treatment Failure at 48 Hours (Two Full Days After Enrollment)
Development of any signs of very severe pneumonia at any time Hypoxemia defined as SpO2 <85% or <80% for altitude < or ≥1500m respectively measured after minimum of 3 minutes on ambient air Persistent vomiting (occurring within 30 minutes of administration of amoxicillin with failure to retain drug after 3 successive attempts at administration) at any time Clinical diagnosis of new bacterial co-morbid condition requiring revision of antibiotic treatment at any time Lower chest wall indrawing Temperature ≥38◦C Respiratory rate ≥5bpm of admission rate if above age-adjusted normal upper limit
Measured: 48 hours

Secondary outcomes (4)

Treatment Failure at or Before Discharge / Day 5 Post Enrollment (Whichever Occurs First)
Treatment failure as defined in the primary outcome measure.
Measured: Patients will be followed up from the day of hospitalisation (day 0) until the day of medical discharge (average duration of 3 days) or until day 5 of hospitalisation (whichever occurs first).
Readmission With Diagnosis of Severe or Very Severe Pneumonia Within 14 Days of Enrollment
Measured: Day 0 to Day 14
Death at or Before Five Days Following Enrollment
Death defined as: in-hospital death occurring at any time after randomisation (recruitment for HIV-exposed participants) or verbal report of death of the enrolled patient from parent/guardian communicated either directly or via telephone conversation.
Measured: Day 0 to Day 5
Outcome (Death/Readmission) at 14 Days as Determined by Telephone or Direct Interview
Definition of death as described in third secondary outcome measure.
Measured: Day 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2011Sep 2013

First posted22 Jul 2011 (estimated)
Study startSep 2011
Primary completionSep 2013
Study completionSep 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for PneumoniaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 561 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01399723
Sponsor's protocol ID: KEMRI_CT_2010/0014
Other IDs: SSC 1911
Status last verified: Jan 2015
First submitted: 12 Jul 2011
Last updated: 13 Feb 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Agweyu A, Gathara D, Oliwa J, Muinga N, Edwards T, Allen E, Maleche-Obimbo E, English M; Severe Pneumonia Study Group. Oral amoxicillin versus benzyl penicillin for severe pneumonia among kenyan children: a pragmatic randomized controlled noninferiority trial. Clin Infect Dis. 2015 Apr 15;60(8):1216-24. doi: 10.1093/cid/ciu1166. Epub 2014 Dec 30.
PubMed 25550349

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 13 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Amoxicillin Versus Benzyl Penicillin for Severe Childhood Pneumonia Amongst Inpatients: An Open Label Randomised Controlled Non-inferiority Trial
ClinicalTrials.gov ID: NCT01399723
Acronym / sponsor ID: KEMRI_CT_2010/0014
Conditions: Pneumonia
Keywords: Severe pneumonia
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 561 participants (actual)
Lead sponsor: KEMRI-Wellcome Trust Collaborative Research ProgramUniversity, hospital or other
Collaborators: University of Oxford, London School of Hygiene and Tropical Medicine, University of Nairobi
Study start: Sep 2011
Primary completion: Sep 2013 (actual)
Study completion: Sep 2013 (actual)
First posted: 22 Jul 2011 (estimated)
Results: Posted 13 Feb 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Amoxicillin 45mg/kg 12 hourly	Experimental	Drug: Amoxicillin
Benzyl Penicillin 50,000IU/kg 6 hourly	Active comparator	Drug: Benzyl penicillin

Who may qualify

Ages: 2 to 59 months
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (2 listed)

Clinical signs of WHO-defined severe pneumonia
Age 2 months to 59 months

Key exclusion criteria (14 listed)

Clinical signs of WHO-defined very severe pneumonia
Clinical or laboratory diagnosis of meningitis
Clinical diagnosis of severe malnutrition (marasmus/kwashiorkor)
Clinical or laboratory diagnosis of severe anaemia requiring transfusion
HIV-exposure on rapid HIV antibody test (only observational data will be collected from these patients)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AmoxicillinOral 45mg/kg 12 hourly	Drug	Amoxicillin 45mg/kg 12 hourly
Benzyl penicillinIntravenous 50,000IU/kg 6 hourly	Drug	Benzyl Penicillin 50,000IU/kg 6 hourly

Primary outcome

Treatment Failure at 48 Hours (Two Full Days After Enrollment)
Time frame: 48 hours
Development of any signs of very severe pneumonia at any time Hypoxemia defined as SpO2 <85% or <80% for altitude < or ≥1500m respectively measured after minimum of 3 minutes on ambient air Persistent vomiting (occurring within 30 minutes of administration of amoxicillin with failure to retain drug after 3 successive attempts at administration) at any time Clinical diagnosis of new bacterial co-morbid condition requiring revision of antibiotic treatment at any time Lower chest wall indrawing Temperature ≥38◦C Respiratory rate ≥5bpm of admission rate if above age-adjusted normal upper limit

4 secondary outcomes

Treatment Failure at or Before Discharge / Day 5 Post Enrollment (Whichever Occurs First)
Time frame: Patients will be followed up from the day of hospitalisation (day 0) until the day of medical discharge (average duration of 3 days) or until day 5 of hospitalisation (whichever occurs first).
Readmission With Diagnosis of Severe or Very Severe Pneumonia Within 14 Days of Enrollment
Time frame: Day 0 to Day 14
Death at or Before Five Days Following Enrollment
Time frame: Day 0 to Day 5
Outcome (Death/Readmission) at 14 Days as Determined by Telephone or Direct Interview
Time frame: Day 14

Results and safety

Results posted to the registry on 13 Feb 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Amoxicillin 45mg/kg 12 Hourly	263	263
Benzyl Penicillin 50,000IU/kg 6 Hourly	264	263

Primary outcome: Treatment Failure at 48 Hours (Two Full Days After Enrollment)

Time frame: 48 hours. Number. Unit: participants

Measure	Amoxicillin n = 263	Penicillin n = 263
Value	20	21

Amoxicillin vs Penicillin: Risk Difference (RD): -0.4 (95% CI -5.0 to 4.2)

Population analysed: Intention to treat analysis

4 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Amoxicillin	1 of 263 (0.4%)	0 of 263 (0%)	Not reported
Benzyl Penicillin	3 of 263 (1.1%)	0 of 263 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 25550349Agweyu A, Gathara D, Oliwa J, Muinga N, Edwards T, Allen E, Maleche-Obimbo E, English M; Severe Pneumonia Study Group. Oral amoxicillin versus benzyl penicillin for severe pneumonia among kenyan children: a pragmatic randomized controlled noninferiority trial. Clin Infect Dis. 2015 Apr 15;60(8):1216-24. doi: 10.1093/cid/ciu1166. Epub 2014 Dec 30.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ambrose Agweyu, MSc principal investigator

Kemri- Wellcome Trust Research Programme, Nairobi, Kenya

Elizabeth Obimbo, MMed principal investigator

Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya

Roma Chilengi, MD principal investigator

Centre for Infectious Disease Research, Zambia

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Amoxicillin and Benzyl penicillin in people with Pneumonia, run by KEMRI-Wellcome Trust Collaborative Research Program at 6 sites in Kenya.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment Failure at 48 Hours (Two Full Days After Enrollment) (time frame: 48 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01399723, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2015.