Can a reduced hospital stay for young infants with possible serious bacterial infection (PSBI) lead to similar or improved treatment outcomes compared to existing WHO guidelines?
| ISRCTN | ISRCTN11693277 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11693277 |
| Secondary identifying numbers | Site Protocol for Uttar Pradesh, India, Version 1.3, 3 June 2020 (Based on WHO Generic Protocol, Version 2.3 - 2 June 2020, Universal Trial Number (UTN): U1111-1251-1576, ERC0003289), CTRI/2020/11/029309 |
- Submission date
- 22/09/2020
- Registration date
- 09/10/2020
- Last edited
- 18/08/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Current WHO guidelines recommend that infants from birth up to 59 days of age with signs of possible serious bacterial infections (PSBI) should be managed in the hospital with injectable antibiotics and supportive care. When a referral to the hospital is not feasible or refused by the family, those with extremely severe signs (no movement at all, unable to feed at all or having convulsions) are categorized as critically ill, and those with less severe signs are classified under clinical severe infection (CSI). CSI can be managed at home on an outpatient/outreach basis with antibiotics.
The study is designed to rigorously assess treatment failure in infants in a uniform, standardized way. The ultimate goal is to evaluate the relative safety of outpatient treatment by comparing rates of treatment failure in hospital vs home care arms in low-risk infants with PSBI.
Who can participate?
Study-1: All young infants aged under 2 months old who have ONLY one of the signs of PSBI.
Study-2: All patients admitted to the study hospitals with higher risk signs of PSBI or two or more signs of CSI.
What does the study involve?
Patients in both studies will be assigned to one of 2 treatment groups i.e. hospital treatment or home treatment. Both groups will receive the same treatment and will be followed up for 15 days.
What are the possible benefits and risks of participating?
There are no additional benefits or risks. The treatment regimens prescribed for both hospital and home care infants are standard antibiotics that are part of existing WHO guidelines and whose safety has already been established.
Where is the study run from?
Community Empowerment Lab, Lucknow (India)
When is the study starting and how long is it expected to run for?
January 2020 to December 2024
Who is funding the study?
World Health Organization (Switzerland)
Who is the main contact?
Dr Vishwajeet Kumar (scientific), vkumar@celworld.org
Dr Yaswant Kumar Rao (public), ykraoneo@yahoo.co.in
Contact information
Scientific
26/11, Wazir Hasan Road
Lucknow
226001
India
 ORCID ID |
0000-0003-1084-7152 |
|---|---|
| Phone | +91 9935689777 |
| vkumar@celworld.org |
Public
Head of Department Pediatrics, GSVM Medical College
Kanpur
208002
India
| Phone | +91 9919080807 |
|---|---|
| ykraoneo@yahoo.co.in |
Study information
| Study design | Open-label two-arm individually-randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Home |
| Study type | Treatment |
| Participant information sheet | ISRCTN11693277_PIS_Study1_V.1_06Apr20.pdf |
| Scientific title | Optimizing place of treatment and antibiotic regimens for young infants presenting with signs of possible serious bacterial infection |
| Study acronym | PSBI |
| Study objectives | Young infants (YIs) with only one low-mortality risk sign (high body temperature ≥38°C or severe chest indrawing or fast breathing of ≥60 breaths per minute in <7 days old infants) of critical severe infection (CSI) presenting to the outpatient/emergency department of a hospital, who receive outpatient treatment, will experience a better, or at least non-inferior, clinical outcome than YIs that receive inpatient treatment. Similarly, among hospital-admitted YIs with a high-mortality risk sign (movement only when stimulated or not feeding well/stopped feeding well or low body temperature (<35.5°C)) or two or more signs of CSI who clinically improve 48 h after initiation of treatment and have a negative C-reactive protein (CRP) laboratory test (Population), does discharge from hospital on oral amoxicillin at home for the next five days (Intervention), compared with continued hospital management for next five days (Control). |
| Ethics approval(s) |
1. Approved 12/06/2020, WHO ERC (20, Avenue Appia, Geneva 27, 1211, Switzerland; +41 22 7912111; nisary@who.int), ref: ERC.0003289 2. Approved 05/07/2020, CEL IEC (26/11, Wazir Hasan Road, Lucknow, 226001, India; +91 (0)522-4932315; irb@cel.org.in), ref: CEL/RES/202007/001 3. Approved 21/07/2020, GSVM ethics committee (Room no. 125, 1st floor, GSVM Medical College, Kanpur, -, India; +91-9454581649; ecgsvm@gmail.com), ref: EC104/July/2020 4. Approved 19/12/2022, SNMC Institutional Ethics Committee, India (Room no-11, 1st floor, Transfusion medicine department, SNMC, Agra, -, India; None provided; ecsnmc20@gmail.com), ref: SNMC/IEC/2022/65 |
| Health condition(s) or problem(s) studied | Critical severe infection (CSI) or critical illness of Possible Serious Bacterial Infection (PSBI) in sick young infants |
| Intervention | Young infants (YIs) <2 months old visiting outpatient clinics or emergency rooms of participating hospitals will be screened for one low-mortality risk sign of CSI (study-1) or one high-mortality risk sign/multiple low-mortality risk sign of CSI (Study-2). For study-1, YIs will be consented and randomised through a sealed envelope for outpatient/home treatment (intervention group) or inpatient/hospital treatment (control group). The outpatient treatment with injectable gentamicin (once daily) for 2 days plus oral amoxicillin (twice daily) for 7 days. The inpatient antibiotic treatment for at least 7 days initiated with WHO recommended antibiotic regimen of injectable ampicillin (four time daily) plus injectable gentamicin (once daily) along with other supportive care. Outcome assessment will be carried by visiting all enrolled young infants on day 2, 4, 8 and 15 after enrolment. Outcome assessment will be conducted at the hospital or at home after discharge in the control arm and at home in the intervention arms. Outcomes will only be ascertained by the IOAs in accordance with the outcomes criteria For study-2, YIs who were admitted at the study hospital with relatively higher-mortality risk signs of CSI at presentation/screening will be assessed for eligibility for this study 48 h after initiation of treatment and considered for inclusion in the study if: i) clinically well on day 3 defined as absence of all signs of critical illness or CSI, and ii) Laboratory test (CRP) negative. They will be randomised using sealed envelope and assigned to intervention or control treatment group. In the intervention group, they will be discharged from hospital and treated at home with oral antibiotics for 5 days. The control group will continue inpatient hospital injectable antibiotic treatment and supportive therapy for a total of 7 days. Outcome assessment will be carried out by visiting all enrolled young infants in the control arm at the hospital or at home after discharge and intervention arm enrolees at home on Day 8 and 15 of initiation of treatment. In both the studies, all YIs will be followed up for 15 days after enrolment. Drug dosages: Gentamicin (strength 20 mg/ml) (Give once a day for 7 days) Weight (kg) Dose (ml) 1.5 – 2.4 0.4 2.5 – 3.9 0.8 4.0 – 5.9 1.2 Ampicillin (strength 250 mg/1.5 ml) (Give 50 mg/kg body weight twice daily for 7 days) Weight (kg) Dose (ml) 1.5 – 2.4 0.8 2.5 – 3.9 1.2 4.0 – 5.9 1.5 Gentamicin (I/M) (strength 20 mg/ml) (Give once a day for 2 days) Weight (kg) Dose (ml) 1.5 – 2.4 0.4 2.5 – 3.9 0.8 4.0 – 5.9 1.2 Amoxicillin (250 mg per dose) (Give twice daily for 7 days) Weight (kg) Dose (tablet) 1.5 – 2.4 0.5 2.5 – 3.9 0.5 4.0 – 5.9 1 |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Gentamicin, amoxicillin, ampicillin |
| Primary outcome measure | Measured using case report forms completed at follow up: Study-1: 1. Death any time from randomization up to day 15 of initiation of therapy 2. Presence of any sign of critical illness (no movement at all, unable to feed at all, or convulsions) or any sign suggestive of another serious infection, e.g. meningitis, bone or joint infection, on day 2, 4 or day 8 of initiation of therapy 3. Presence of any new sign of CSI on day 4 or day 8 of initiation of therapy 4. Persistence of the presenting sign on day 8 of the initiation of therapy Study-2: 1. Death between randomization (day 3 of initiation of therapy) and day 15 of initiation of therapy 2. Presence of any sign of critical illness (no movement at all, unable to feed at all, or convulsions) or any sign suggestive of another serious infection, e.g. meningitis, bone or joint infection, on day 8 of initiation of therapy 3. Presence of any sign of CSI on day 8 of initiation of therapy |
| Secondary outcome measures | There are no secondary outcome measures |
| Overall study start date | 01/01/2020 |
| Completion date | 31/12/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Neonate |
| Upper age limit | 2 Months |
| Sex | Both |
| Target number of participants | Study-1: 7,000 infants. Study-2: 5,250 infants |
| Total final enrolment | 12250 |
| Key inclusion criteria | Study-1: 1. Aged <2 months 2. Living in a geographic area where follow-up for 14 days can be accomplished presenting to outpatient clinics or emergency rooms of participating hospitals 3. ONLY one of the following low-risk signs of PSBI: 3.1. Body temperature ≥38°C 3.2. Severe chest indrawing 3.3. Fast breathing (infants aged <7 days) Study-2: 1. Aged <2 months 2. Admitted to the study hospitals with relatively higher-mortality risk signs of CSI at presentation (not feeding well, movement only on stimulation, low body temperature <35.5°C, two or more of the six signs of CSI) 3. Clinically well on day 3 defined as absence of all signs of critical illness (not feeding at all, no movement at all, convulsions) or CSI (not feeding well, movement only when stimulated, low body temperature (<35.5°C, high body temperature (≥38°C), severe chest indrawing, fast breathing in <7 days old) 4. Laboratory test negative 5. Family lives within a catchment area where a follow-up of up to day 15 can be accomplished |
| Key exclusion criteria | Current exclusion criteria as of 17/10/2022: Study-1: 1. Weight <2 kg at the time of presentation (if age at screening is less than 10 days) or weight for age <-3z 2. Appearance of low-mortality risk signs in first 24 h of life 3. Signs of critical illness (no movement at all, unable to feed at all, convulsions) 4. Signs of CSI associated with a high risk of mortality (stopped feeding well, movement only on stimulation, low body temperature < 35.5°C or two or more of the six signs of CSI) 5. Any sign suggestive of another serious illness/condition, such as major congenital malformations, severe jaundice, conditions requiring major surgery, meningitis, bone or joint infection, severe dehydration, etc. 6. Hospitalized for any illness in the previous 2 weeks 7. Prior use of injectable antibiotics for the same illness in the last 2 days excluding pre-referral dose 8. Previously included in this study or currently included in any other study Study-2: 1. Weight <2 kg at the time of presentation (if age at screening is less than 10 days) or weight-for-age <-3z 2. Signs of critical illness on admission (no movement at all, unable to feed at all, or convulsions) 3. Appearance of any high-mortality risk sign or multiple low-mortality risk signs in first 24 h of life 4. Hospitalized for any illness in the previous 2 weeks 5. Prior use of injectable antibiotics for the same illness 6. Previously included in this study or currently included in any other study 7. Any other reason to stay in hospital, as decided by the treating physician _____ Previous exclusion criteria: Study-1: 1. Weight <2 kg at the time of presentation (if age at screening is less than 10 days) or weight for age <-3z 2. Appearance of low-mortality risk signs in first 24 h of life 3. Signs of critical illness (no movement at all, unable to feed at all, convulsions) 4. Signs of CSI associated with a high risk of mortality (stopped feeding well, movement only on stimulation, low body temperature < 35.5°C or two or more of the six signs of CSI) 5. Any sign suggestive of another serious illness/condition, such as major congenital malformations, severe jaundice, conditions requiring major surgery, meningitis, bone or joint infection, severe dehydration, etc. 6. Hospitalized for any illness in the previous 2 weeks 7. Prior use of injectable antibiotics for the same illness 8. Previously included in this study or currently included in any other study Study-2: 1. Weight <2 kg at the time of presentation (if age at screening is less than 10 days) or weight-for-age <-3z 2. Signs of critical illness on admission (no movement at all, unable to feed at all, or convulsions) 3. Appearance of any high-mortality risk sign or multiple low-mortality risk signs in first 24 h of life 4. Hospitalized for any illness in the previous 2 weeks 5. Prior use of injectable antibiotics for the same illness 6. Previously included in this study or currently included in any other study 7. Any other reason to stay in hospital, as decided by the treating physician |
| Date of first enrolment | 07/10/2021 |
| Date of final enrolment | 10/08/2024 |
Locations
Countries of recruitment
- India
Study participating centres
Gomti Naga
Lucknow
226010
India
Kanpur
208002
India
Shiwala
Patkapur
Kanpur
208001
India
Kanpur
208001
India
Agra
282002
India
Sponsor information
Other
Department of Maternal, Newborn, Child and Adolescent Health
World Health Organization
20 Avenue Appia
Geneva
27
Switzerland
| Phone | +41 22 7912111 |
|---|---|
| nisary@who.int | |
| Website | http://www.who.int/countries/che/en/ |
"ROR" |
https://ror.org/01f80g185 |
Funders
Funder type
Research organisation
Private sector organisation / International organizations
- Alternative name(s)
- منظمة الصحة العالمية, 世界卫生组织, Всемирная организация здравоохранения, Organisation mondiale de la Santé, Organización Mundial de la Salud, WHO, 世卫组织, ВОЗ, OMS
- Location
- Switzerland
Results and Publications
| Intention to publish date | 31/03/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. |
| IPD sharing plan | All data generated or analysed during this study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | 06/04/2020 | 13/10/2020 | No | Yes | |
| Participant information sheet | 06/04/2020 | 13/10/2020 | No | Yes | |
| Participant information sheet | 06/04/2020 | 13/10/2020 | No | Yes | |
| Protocol file | version v1.3 | 03/06/2020 | 13/10/2020 | No | No |
Additional files
- ISRCTN11693277_PIS_Study1_V.1_06Apr20.pdf
- Uploaded 13/10/2020
- ISRCTN11693277_PIS_Infants_V.1_06Apr20.pdf
- Uploaded 13/10/2020
- ISRCTN11693277_PIS_Study2_V.1_06Apr20.pdf
- Uploaded 13/10/2020
- ISRCTN11693277_PROTOCOL_v1.3_3June2020.pdf
- Uploaded 13/10/2020
Editorial Notes
18/08/2024: The following changes were made:
1. CTRI ID added.
2. The total final enrolment was changed from 12220 to 12250.
3. The recruitment end date was changed from 15/08/2024 to 10/08/2024.
15/07/2024: The following changes were made:
1. The overall study end date was changed from 30/09/2024 to 31/12/2024.
2. The total final enrolment was changed from 8002 to 12220.
3. The recruitment end date was changed from 30/06/2024 to 15/08/2024.
13/10/2023: The following changes have been made:
1. The recruitment end date was changed from 31/10/2023 to 30/06/2024.
2. The overall study end date was changed from 30/06/2024 to 30/09/2024.
3. The intention to publish date was changed from 31/03/2024 to 31/03/2025.
4. Ethics approval from SNMC Institutional Ethics Committee, India was added.
5. The study participating centre Sarojani Nayadu Medical College was added.
11/07/2023: The following changes were made to the study record:
1. The overall study end date was changed from 31/03/2024 to 30/06/2024.
2. The intention to publish date was changed from 01/01/2023 to 31/03/2024.
3. Total final enrolment added.
17/10/2022: The following changes have been made:
1. The recruitment start date has been changed from 01/01/2021 to 07/10/2021.
2. The recruitment end date has been changed from 31/10/2022 to 31/10/2023.
3. The overall trial end date has been changed from 31/12/2022 to 31/03/2024 and the plain English summary updated accordingly.
4. The participant exclusion criteria have been changed.
5. Dufferin Women's Hospital and Shyam Children & Maternity Centre have been added to the trial participating centres.
13/10/2020: The participant information sheets have been uploaded. Uploaded protocol Version 1.3, 3 June 2020 (not peer reviewed).
01/10/2020: Trial’s existence confirmed by World Health Organisation Research Ethics Committee
