mason: simplified management of infections in neonates & young infants for use in outpatient &...

7/28/2019 Mason: Simplified Management of Infections in Neonates & Young Infants for Use in Outpatient & Community Settings

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Global Newborn Health Conference, South Africa April 20131 |

Simplified management of infections in neonates and young

infants for use in outpatient and community settings -

A multicentre randomised controlled trial in

DR Congo, Kenya and Nigeria

Elizabeth Mason

On behalf of the African Neonatal Sepsis Trial (AFRINEST) Group

Johannesburg, April 2013

Department of Maternal, Newborn, Child and Adolescent Health


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AFRINEST Investigator Group

Democratic Republic of Congo (DRC)

Prof. Antoinette Kitoto Tshefu, University of Kinshasa, School of Public Health

Kenya

Prof. Fabian Esamai, Moi University School of Medicine, Child Health and Paediatrics.

Nigeria

Dr Adejumoke Ayede, University of Ibadan, College of Medicine

Prof. Ebunoluwa A. Adejuyigbe, Obafemi Awolowo University Ile-Ife, Paediatrics. Prof. Robinson D. Wammanda, Ahmadu Bello University, Zaria, Paediatrics


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Study Sites

DRC Kenya Nigeria

Site Equateur

Province

Western

province

Ibadan, Ile-

Ife, Zaria

Study

population

300,000

2 districts

350,000

8 districts

600,000

5 LGAs*

Expected

Births/year

12,000 12500 25,000

Expected sick

infants/year

2000 2000 3000

*LGA: Local government authority

Gemena, DRC


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Primary Objective

To evaluate simple, safe and effective antibiotic

regimens for use at first level facilities and in the

community for young infants with possible serious

bacterial infection whose families do not accept or

cannot access referral level care.


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Context: Research in programme setting

Sick young infants seen by

trained health workers

IMCI assessment and management

Possible Severe Bacterial Infection (PSBI)

2: Home based care1: Facility based care

Facility births Home birthsCHWs

Find births

Make home visits to:

identify signs of illness

empower families to identify signs

of illness and promote care seeking

Referral not accepted

3: IMCI

No illness

Normal or mild illness

(treated)

Referral to hospitalaccepted

Home care


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Study Design: Randomized trialOpen-label equivalence with two strata

Referral not accepted

Clinical severe infection Fast breathing only

Treated with simplified antibiotic regimens on

outpatient basis Outpatientman

agement

Consent given and enrolled

Critically ill

Offered simplified antibiotic

regimen

4: Current research

Not enrolled


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Inclusion and exclusion criteria

Inclusion criteria

Study I: Clinical severe infection

One or more of the following signs:

stopped feeding well

movement only when stimulated

severe chest in-drawing

Temperature >38.0oC or


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Treatment regimens

Control arm for both studies

A (reference treatment): IM gentamicin and procaine penicillin once daily for 7 days

14 injections

Experimental interventions

Clinical severe infection

B: IM gentamicin once daily and oral amoxicillin twice daily for 7 days

7 injections

C: IM gentamicin and procaine penicillin once daily for 2 days, thereafteroral amoxicillin twice daily for 5 days 4 injections

D: IM gentamicin once daily and oral amoxicillin twice daily for 2 days, thereafteroral amoxicillin twice daily for 5 days 2 injections

Fast breathing

E: oral amoxicillin twice daily for 7 days No injections


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Outcomes

Primary outcome Treatment failure within 7 days of randomization (includes death)

Secondary outcomes

Death between 8-15 days of enrolment

Relapse of signs/symptoms present at enrolment

Compliance to study therapy

Adverse effects due to study drugs

Independent outcome assessment

Scheduled on days 4, 8, 11 and 15

Additionally when treatment health workers feels the need


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Treatment Failure - Clinical Severe InfectionIN THE FIRST WEEK AFTER RANDOMIZATION

Death

Hospitalization

Serious adverse effect of the study antibiotics

Clinical deterioration defined as emergence of any sign of critical illnessor a new sign of severe infection

No improvement by day 4

Re-emergence of any presenting sign after disappearance on day 4

Persistence of a presenting sign on day 8


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Treatment Failure - Fast BreathingIN THE FIRST WEEK AFTER RANDOMIZATION

Death

Hospitalization

Serious adverse effect of the study antibiotics

Clinical deterioration defined as emergence of any sign of critical illnessor a new sign of severe infection

No improvement in respiratory rate by day 4

Persistence of fast breathing on day 8


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Sample size

Clinical severe infection - 3600 in 3 countries

Fast Breathing - 2300 in 3 countries

Duration of study: 30 months


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Current status of study

Surveillance NumberBirths identified 77,589

Infants identified by CHW to have any sign of infection 11,625

Infants assessed by nurses to have signs of Possible

Serious Bacterial Infection

6918

Infants not enrolled because of critical illness 467

Infants not enrolled because of another reason 985

Infants with clinical severe infection enrolled in the

study

3335

Infants with fast breathing enrolled in the study 2131


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Policy implications

Simplest safe and effective regimens for outpatient treatment ofclinical severe infection, where referral is not possible

Simplest safe and effective treatment of fast breathing

Role of CHWs in identifying signs of infection at home, and takinginfants for treatment to nearest health facility

Health system requirements planning, human resources,

commodities, supervision and monitoring for outpatient

treatment of severe infections


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Next Steps

Complete enrolment of the study May 2013

Complete follow-up & data collection June 2013

Data entry completion and cleaning July to August 2013

Data analysis and report writing September 2013

Dissemination of the results November 2013


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Other members of Study Group

Democratic Republic of Congo

Dr. Cyril Engmann Dr Adrien L. Longombe

Kenya Dr. Peter Gisore Prof. Edward Liechty Dr. Sherri Bucher

Nigeria

Ibadan

Prof. A. Falade Prof. A. Sowunmi Prof. E.A. Bamgboye Mr. K. A. Ogedengbe

Ile Ife Prof. A. Odebiyi Dr. O. Esimai Dr H.C Anyabolu

Zaria Prof. W. Ogala Dr Clara Ejembi

Data Management: London School of Hygiene and TropicalMedicine, London (Lu Gram and Simon Cousens)

Technical Support and Coordination: Department ofMaternal, Newborn, Child & Adolescent Health, WHO Geneva

(S. Qazi, R. Bahl, N. Rollins, S. Yoshida)

Funding: Bill and Melinda Gates Foundation through WHO

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