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Trial registered on ANZCTR


Registration number
ACTRN12617001373369
Ethics application status
Approved
Date submitted
13/07/2017
Date registered
27/09/2017
Date last updated
27/09/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Implementation of an innovative approach to jump start simplified management of sick young infants with possible serious bacterial infection (PSBI) where referral is not feasible for potential scale-up
Scientific title
Implementation of an innovative approach to jump start simplified management of sick young infants with possible serious bacterial infection (PSBI) where referral is not feasible for potential scale-up
Secondary ID [1] 292428 0
Nil unknown
Universal Trial Number (UTN)
Trial acronym
PSBI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Possible Serious Bacterial Infection 304025 0
Condition category
Condition code
Infection 303355 303355 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
WHO developed a guideline ‘managing possible serious bacterial infection in young infants when referral is not feasible’ in 2015. This guideline will make treatment more accessible and acceptable to families, as well as easier and less costly for the system to implement, when referral is not feasible. Following are the WHO recommendations on managing PSBI in young infants 0-59 days old when families do not accept or cannot access referral care:
1. Community health workers and home visits for postnatal care: At home visits made as part of postnatal care, community health workers should counsel families on recognition of danger signs, assess young infants for danger signs of illness and promote appropriate care seeking. Community health workers should conduct once every week for 2 months post birth.
2. Infants 0–6 days with fast breathing as the only sign of illness: Young infants 0–6 days old with fast breathing as the only sign of illness should be referred to hospital. If families do not accept or cannot access referral care, these infants should be treated with oral amoxicillin, 50 mg/kg per dose twice daily for seven days, by an appropriately trained health worker.
3. Infants 7–59 days with fast breathing as the only sign of illness: Young infants 7–59 days old with fast breathing as the only sign of illness should be treated with oral amoxicillin, 50 mg/kg per dose twice daily for seven days, by an appropriately trained health worker. These infants do not need referral.
4. Young infants 0–59 days old with clinical severe infection: Young infants 0–59 days old with clinical severe infection whose families do not accept or cannot access referral care should be managed in outpatient settings by an appropriately trained health worker with one of the following regimens:
Option 1: Intramuscular gentamicin 5–7.5 mg/kg (for low-birth-weight infants gentamicin 3–4 mg/kg) once daily for seven days and twice daily oral amoxicillin, 50 mg/kg per dose for seven days. Close follow-up is essential.
Option 2: Intramuscular gentamicin 5–7.5 mg/kg (for low-birth-weight infants gentamicin 3–4 mg/kg) once daily for two days and twice daily oral amoxicillin, 50 mg/kg per dose for seven days. Close follow-up is essential. A careful assessment on day 4 is mandatory.
5. Young infants 0–59 days old with critical illness: Young infants 0–59 days old who have any sign of critical illness (at presentation or developed during treatment of clinical severe infection) should be hospitalized after pre-referral treatment (Pre-referral treatment: Give first dose of both ampicillin (50 mg/kg per dose) or benzyl penicillin (50000 units/kg per dose) and gentamicin (5–7.5 mg/kg per dose) intramuscularl).
We propose an implementation research for the implementation of an innovative approach to spearhead facilitated policy adoption and readiness for scale up for routine use of simplified management of sick young infants with possible serious bacterial infection (PSBI) where referral is not feasible through the following.
• Policy dialogue and orientation meetings held at national level with Ministry of Health (MOH) and other stakeholders at national and sub-national level to discuss limited policy adoption to set up demonstration sites to deliver this intervention and potential scale-up in programme setting.
• Demonstration sites established in the five countries to demonstrate feasibility of delivering simplified antibiotic regimens to young infants with PSBI where referral is not feasible and following them till day 14 for outcome; and develop a partnership with programme managers to provide technical assistance to initiate a pilot in a few health facilities in programme setting. Demonstration sites are first level public health facilities.
The intervention will be deliver in a routine setting at first level care facilities in the participating countries. Routine monitoring and supervision through Department/Ministry of Health will continue. The health workers will be trained by the Ministry of Health in these guidelines before the commencement of actual enrolment. Data will be extracted from the routine patient registration forms placed at the participating centres. The outcome will be assessed as number of young infants with PSBI refusing referral advice to the hospital during the study period.
The exact medication regimen administered to each patient who does not require/accept referral will be at the clinical discretion of the treating health worker. The duration of intervention will be 18 months at each site.
The young infant IMCI materials will be revised to include the new WHO recommendations for PSBI. These include a chart booklet, a facilitator’s guide, participant training manual, data collection instruments and other ancillary documents.
A training of trainers’ (TOT) for revised young infant component of IMCI will be held in each country. It will be facilitated by WHO and IMCI master trainers in each country. Participants will be trained on revised IMCI modules for sick young infants during the first 3 days and the fourth day will be used to review site preparation and review the implementation research study materials.
Master trainers trained in training of trainers will impart a 7-day training to health workers posted at the first level health facility to identify young infants with PSBI. It contains classroom training as well as clinical sessions. A one-day refresher training will be given to physicians also. In each training batch 20-25 health workers will be trained.
Intervention code [1] 298605 0
Treatment: Drugs
Intervention code [2] 298886 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302744 0
Number of young infants with possible serious bacterial infection (PSBI) refusing referral advice to the hospital
To assess the primary outcome, data will be collected from patient registration forms kept at the health facilities.
Timepoint [1] 302744 0
18 months (data collection phase of the study)
Secondary outcome [1] 336890 0
At each site principal investigators will collect and share the information on barriers and facilitator factors in implementation of an innovative approach to jump start simplified management of sick young infants with possible serious bacterial infection (PSBI) where referral is not feasible for potential scale-up. The information will be collected through conducted in-depth interview and directly observing some of the practices of health providers.
Timepoint [1] 336890 0
18 months (data collection phase of the study)
Secondary outcome [2] 336891 0
Number of young infants with possible serious bacterial infection (PSBI) accepting simplified antibiotic regimen treatment on outpatient basis.
To assess the secondary outcome, data will be collected from patient registration forms kept at the health facilities.
Timepoint [2] 336891 0
14 days after initiation of treatment

Eligibility
Key inclusion criteria
Young infants 0-59 days with PSBI and whose families do not accept or cannot access referral care for treatment. Clinical signs of PSBI are defined as:
• fast breathing (respiratory rate greater and equal to 60 breaths/minute)
• severe chest in-drawing
• fever (temperature greater and equal to 38 °C)
• hypothermia (temperature less than 35.5 °C)
• no movement at all or movement only on stimulation
• feeding poorly or not feeding at all
• convulsions.
Presence of any one of above mentioned signs
Minimum age
No limit
Maximum age
59 Days
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
none.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 9054 0
Ethiopia
State/province [1] 9054 0
Country [2] 9055 0
India
State/province [2] 9055 0
Country [3] 9056 0
Nigeria
State/province [3] 9056 0
Country [4] 9057 0
Pakistan
State/province [4] 9057 0

Funding & Sponsors
Funding source category [1] 296987 0
Charities/Societies/Foundations
Name [1] 296987 0
Bill and Melinda Gates Foundation
Address [1] 296987 0
500 Fifth Avenue North
Seattle, WA 98109
Country [1] 296987 0
United States of America
Primary sponsor type
Other
Name
World Health Organization
Address
Avenue Appia 20, Geneva 1211
Country
Switzerland
Secondary sponsor category [1] 295989 0
None
Name [1] 295989 0
Address [1] 295989 0
Country [1] 295989 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298186 0
WHO ERC
Ethics committee address [1] 298186 0
Avenue Appia 20, Geneva 1211
Ethics committee country [1] 298186 0
Switzerland
Date submitted for ethics approval [1] 298186 0
12/06/2015
Approval date [1] 298186 0
14/08/2015
Ethics approval number [1] 298186 0
MCA00415

Summary
Brief summary
The purpose of this work is to inform and accelerate the use of simplified management of sick young infants up to two months of age with possible serious bacterial infection (PSBI) for eventual scale up at country level in selected countries in Africa and Asia.
Infections including pneumonia, sepsis and meningitis in infants below two months of age (young infants) caused over 640,000 deaths in 2013. The World Health Organization (WHO) has proposed a classification of “possible serious bacterial infection” (PSBI) for infants 0-59 days of age who have fever, low body temperature, fast breathing, severe chest indrawing, not feeding well, convulsions, and no spontaneous movements. An estimated 6.9 million episodes of PSBI occurred in 2012. As these children are at high risk of mortality, WHO recommends hospitalization and treatment with injectable antibiotics for at least 7-10 days. In many low resource settings such inpatient care is neither feasible nor acceptable for many families.
A few descriptive studies have reported management of sick neonates or young infants with simple antibiotic regimens at community or first level health facility where referral was not possible. These treatment regimens were not compared with any reference therapy. Additionally regimen including oral cotrimoxazole was shown to be inferior in efficacy. To address this evidence gap, AFRINEST/SATT studies were undertaken in Bangladesh, Democratic Republic of Congo, Kenya, Nigeria and Pakistan. Their results show that when hospitalisation is not possible, the management of serious infections in young infants can be significantly simplified and effectively delivered near their homes. WHO developed a guideline ‘managing possible serious bacterial infection in young infants when referral is not feasible’ in 2015. This guideline will make treatment more accessible and acceptable to families, as well as easier and less costly for the system to implement, when referral is not feasible.
However, before countries can use implement the guideline at scale, more work is needed to address adoption of policy and implementation and operational issues. It will require a dialogue with policy makers and other stakeholders at country level to facilitate the policy adoption and put in place the enabling environment for implementation. The programme managers will need technical support from experts who have experience in delivering these interventions for development and implementation of operational plans in programme setting. If this work regarding policy dialogue and small scale demonstration projects is not supported at country level, it is unlikely that this important intervention will be adopted as policy, and scaled up.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76258 0
Dr Shamim Ahmad Qazi
Address 76258 0
Department of Maternal, Newborn, Child and Adolescent Health
World Health Organization
Avenue Appia 20, Geneva 1211
Country 76258 0
Switzerland
Phone 76258 0
+41227912547
Fax 76258 0
+41227914853
Email 76258 0
qazis@who.int
Contact person for public queries
Name 76259 0
Dr Shamim Ahmad Qazi
Address 76259 0
Department of Maternal, Newborn, Child and Adolescent Health
World Health Organization
Avenue Appia 20, Geneva 1211
Country 76259 0
Switzerland
Phone 76259 0
+41227912547
Fax 76259 0
+41227914853
Email 76259 0
qazis@who.int
Contact person for scientific queries
Name 76260 0
Dr Shamim Ahmad Qazi
Address 76260 0
Department of Maternal, Newborn, Child and Adolescent Health
World Health Organization
Avenue Appia 20, Geneva 1211
Country 76260 0
Switzerland
Phone 76260 0
+41227912547
Fax 76260 0
+41227914853
Email 76260 0
qazis@who.int

No information has been provided regarding IPD availability
Summary results
No Results