Active prevention and treatment of maternal sepsis in health care facilities in Malawi and Uganda
| ISRCTN | ISRCTN42347014 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN42347014 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Protocol serial number | UoL001663 |
| Sponsor | University of Liverpool |
| Funder | UK Research and Innovation Joint Global Health Trials Grant ref: MRV005782/1 |
- Submission date
- 19/08/2022
- Registration date
- 10/10/2022
- Last edited
- 03/10/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Every 4 minutes, a mother dies from a sepsis-related cause somewhere in the world, with the greatest burden borne by women in Low-Middle Income Countries (LMICs). The Active Prevention and Treatment of Maternal Sepsis (APT-Sepsis) is a carefully developed programme designed specifically to be used in countries and facilities where there are limited resources available. It aims to change health care workers' behaviours to ensure mothers get the best care possible to better prevent and manage infections. APT-Sepsis involves 60 hospital facilities (30 in Malawi and 30 in Uganda). Each facility will be a cluster from which baseline (starting) data will be collected before the start of the APT-sepsis intervention. Then 30 clusters (15 in each country) will be randomised for the APT-sepsis intervention, the remaining sites will continue with their usual practices. The study will evaluate if running the APT-sepsis programme is effective at reducing infection-related maternal death and disease burden. Process evaluation will also be conducted to understand how the programme works in practice and its cost-effectiveness.
Who can participate?
Health care facilities offering maternity care will be included as a cluster following completion of a successful feasibility report requiring the minimum prerequisites of a minimum of 1500 births per year and they provide comprehensive emergency obstetric care. Staff who are invited to complete the interviews and surveys will be healthcare workers who are responsible for the care of pregnant or postnatal women and who are willing to participate.
What does the study involve?
Clusters will be randomised to the study intervention or the control group. The intervention is a training programme that brings together evidence-based practice for the prevention of maternal sepsis. The study will evaluate the effectiveness of the intervention by measuring the incidents of severe infection, maternal deaths and near misses before and after randomisation. The study will also evaluate the staff experience, measuring their acceptability and compliance with the intervention through interviews, surveys and observations. Sites in the control group will also be evaluated to see if their practice changes. Following the completion of the project, all participating sites will be offered the opportunity to receive the training.
What are the possible benefits and risks of participating?
In this study, the Clusters (hospital facilities) are the participants. Providing the APT-Sepsis programme training to staff will improve their knowledge and understanding of the prevention, identification and treatment of maternal sepsis and consequently reduce cases of maternal sepsis in their cluster. These are evidence-based practices (treatments which have been previously researched) to reduce maternal sepsis, therefore the risks are low.
Where is the study run from?
Liverpool Clinical Trials Centre, the University of Liverpool (United Kingdom)
When is the study starting and how long is it expected to run for?
February 2021 to October 2025
Who is funding the study?
This project is supported by the Joint Global Health Scheme (United Kingdom)
Who is the main contact?
Sonia Whyte (United Kingdom)
apt-sepsis@liverpool.ac.uk
Contact information
Public
Liverpool Clinical Trials Centre
University of Liverpool
Liverpool
L69 3BX
United Kingdom
 ORCID ID |
0000-0003-0878-4244 |
|---|---|
| Phone | +44 (0)151 795 8751 |
| apt-sepsis@liverpool.ac.uk |
Principal investigator
Malawi-Liverpool-Wellcome Trust research institute
Queen Elizabeth Central Hospital
College of Medicine
P.O. Box 30096
Chichiri, Blantyre
3
Malawi
| ORCID ID |
0000-0002-7878-2327 |
|---|---|
| Phone | +265 (0)1812423 |
| david.lissauer@liverpool.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Cluster-randomized hybrid-implementation effectiveness study |
| Secondary study design | Cluster randomised trial |
| Study type | Participant information sheet |
| Scientific title | The Active Prevention and Treatment of Maternal Sepsis: A cluster randomised, hybrid implementation effectiveness trial, to improve prevention and management of maternal sepsis in health care facilities in Malawi and Uganda |
| Study acronym | APT-Sepsis |
| Study objectives | To examine the implementation of the APT-Sepsis programme and understand if it is effective at reducing infection related maternal mortality and severe morbidity in resource limited settings. |
| Ethics approval(s) | 1. Approved 13/07/2022, College of Medicine Research and Ethics Malawi (Private Bag 360), Chichiri Blantyre 3 , (Blantyre, Blantyre, 3, Malawi; 265 187 4377; mandal@medcol.mw), ref: 3635 2. Approved 24/02/2023, Uganda National Council for Science and Technology (Plot 6, PO Box 6884, , Kampala, x, Uganda; 256 414 707700; info@uncst.go.ug), ref: HS2613ES 3. Approved 07/09/2022, University of Liverpool, Central University Research Ethics Committee D (Brownlow Hill,, Liverpool, L69 7ZX , United Kingdom; 0151; ethics@liv.ac.uk), ref: 11309 4. Approved 08/12/2022, Infectious Diseases Institute Research Ethics Committee (IDI-REC office, Mulago, 12345,, Milago, 12345, Uganda; +256 39 319 3144; rec@idi.co.ug), ref: 022/2022 5. Approved 26/01/2023, WHO/HQ/FWC/RHR (20, Avenue Appia, Geneva, CH-1211, Switzerland; 41 22 791 4171; reproductivehealth@who.int), ref: A66039 |
| Health condition(s) or problem(s) studied | Maternal Sepsis |
| Intervention | The APT-Sepsis intervention brings together evidence-based practice to address maternal sepsis prevention and treatment via an integrated programme with three interventional domains and an implementation strategy. 1.The first interventional domain is ‘hand hygiene’, ensuring compliance with the WHO 5 movements of hand hygiene. 2. The second interventional domain is infection prevention and management and ensures adoption of evidence-based practices for infection prevention in maternity, including appropriate antibiotic prophylaxis for high-risk women and improved surgical practices. 3. The third interventional domain is better sepsis management and consists of ensuring consistent measurement of patient vital signs and when there is suspected sepsis the triggering of the FAST-M maternal sepsis bundle. This bundle includes Fluids, Antibiotics, Source control, Transfer and Monitoring. |
| Intervention type | Behavioural |
| Primary outcome measure(s) |
Composite outcome of infection-related maternal mortality, infection-related maternal near-miss and severe infection-related morbidity (deep surgical site infection or body cavity infection) measured by the collection of daily observations from routine health facility records from all women who are admitted to the healthcare facility, during pregnancy or within 42 days of delivery with a severe infection from the baseline phase to the end of cluster participation |
| Key secondary outcome measure(s) |
1. Effectiveness of the APT-Sepsis programme to reduce the secondary clinical outcomes of stillbirth, early neonatal death (infection-related and total), maternal mortality (any cause), and a maternal near miss (any cause) measured using daily observations of the routine health facility records from the baseline phase to the end of cluster participation |
| Completion date | 31/07/2025 |
Eligibility
| Participant type(s) | Other |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 172560 |
| Total final enrolment | 431394 |
| Key inclusion criteria | Cluster: Health care facilities offering maternity care, will be included as a cluster following the completion of a successful feasibility report requiring the minimum prerequisites of: 1. A minimum of 1500 births per year 2. Providers of comprehensive emergency obstetric care (e.g., able to perform caesarean sections and blood transfusions) 3. Completed the site readiness assessment process Research participant: Healthcare workers and managers responsible for the care of women during or after pregnancy in the study facility |
| Key exclusion criteria | Cluster exclusion criteria: Facilities not willing to participate in the study Research participant exclusion criteria: Healthcare workers not willing to consent to participation |
| Date of first enrolment | 13/11/2022 |
| Date of final enrolment | 24/06/2025 |
Locations
Countries of recruitment
- Malawi
- Uganda
Study participating centres
Balaka
302100
Malawi
Chikwawa
315100
Malawi
Chiradzulu
306100
Malawi
Dedza
209100
Malawi
Mzimba
104104
Malawi
Phalombe
307100
Malawi
Karonga
102100
Malawi
Kasungu
201300
Malawi
Liwonde
303100
Malawi
Thyolo
310111
Malawi
Mangochi
301400
Malawi
Mchinji
205100
Malawi
Mangochi
301109
Malawi
Dedza
209104
Malawi
Mulanje
308100
Malawi
Mulanje
308104
Malawi
Mwanza
314100
Malawi
Mzimba
104100
Malawi
Nkhatabay
106100
Malawi
Lilongwe
206111
Malawi
Nkhotakota
202100
Malawi
Nsanje
316100
Malawi
Ntcheu
210100
Malawi
Ntchisi
203100
Malawi
Rumphi
103100
Malawi
Salima
208100
Malawi
Namitete Lilongwe
206115
Malawi
Chilema
304102
Malawi
Thyolo
310100
Malawi
Arua
-
Uganda
Koboko
-
Uganda
Adjumani
-
Uganda
Nebbi
-
Uganda
Arua City
-
Uganda
Moyo
-
Uganda
Mukono
-
Uganda
Lugazi
-
Uganda
Jinja
-
Uganda
Bugiri
-
Uganda
Kamuli
-
Uganda
Iganga
-
Uganda
Mbale
-
Uganda
Luwero
-
Uganda
Nakaseke
-
Uganda
Kiboga
-
Uganda
Masindi
-
Uganda
Kigumba
-
Uganda
Lira
-
Uganda
Soroti
-
Uganda
Gulu
-
Uganda
Fortportal
-
Uganda
Kyejonjo
-
Uganda
Mubende
-
Uganda
Kyotera
-
Uganda
Mpigi
-
Uganda
Tororo
-
Uganda
Pallisa
-
Uganda
Kumi
-
Uganda
Katawi
-
Uganda
Phalombe
307100
Malawi
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | At the end of the trial, after the primary results have been published, the anonymised individual participant data (IPD) and associated documentation (e.g., protocol, statistical analysis plan, annotated blank CRF) will be prepared to be shared with external researchers. All requests for access to the IPD will be reviewed by an internal committee at the CTU and discussed with the Chief Investigator in accordance with the CTU policy on data sharing. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Protocol file | Malawi version 6.0 |
07/11/2024 | 09/04/2025 | No | No |
| Protocol file | Uganda version 3.0 |
07/11/2024 | 09/04/2025 | No | No |
| Statistical Analysis Plan | version 2.0 | 04/08/2025 | 26/09/2025 | No | No |
| Statistical Analysis Plan | version 1.0 | 23/07/2025 | 26/09/2025 | No | No |
Additional files
- ISRCTN42347014_PROTOCOL_Uganda_V3.0_07Nov24.pdf
- Uganda
- ISRCTN42347014_PROTOCOL_Malawi_V6.0_07Nov24.pdf
- Malawi
- ISRCTN42347014 APT-SEPSIS_Statistical Analysis Plan_04082025_V2.0.pdf
- Statistical Analysis Plan
- ISRCTN42347014 APT-SEPSIS_ Statistical Analysis Plan_23Jul2025_V1.0.pdf
- Statistical Analysis Plan
Editorial Notes
03/10/2025: The Total Final Enrolment was changed from 514394 to 431394 (Clusters: 59 (431,394 women), Staff interviews: 72).
26/09/2025: The following changes were made to the trial record:
1. The completion date was changed from 31/10/2025 to 31/07/2025.
2. The statistical analysis plan v1.0 was uploaded as an additional file.
3. The statistical analysis plan v2.0 was uploaded as an additional file.
4. The date of final enrolment was changed from 30/04/2025 to 24/06/2025.
22/05/2025: Total final enrolment added.
09/04/2025: Protocols uploaded.
10/02/2025: The following changes were made to the trial record:
1. The ethics approval was added.
2. The overall end date was changed from 31/07/2024 to 31/10/2025.
3. The recruitment end date was changed from 31/07/2024 to 30/04/2025.
4. The study participating centres Lisungwi Community Hospital, Mlambe Mission hospital, Pirimiti Mission Hospital, Midigo HC4, River Oli HC4 were removed and Phalombe district hospital was added.
04/09/2023: The study participating centres were updated to remove Kisenyi HC4, Kawala HC4, Kasangati HC4, Wakiso HC4, Ndejje HC4, Namayumba HC4, and add Kalisizo General Hospital, Gombe General Hospital, Tororo General Hospital, Pallisa General Hospital, Atutur General Hospital, Katakwi General Hospital.
23/01/2023: Kyejonjo General Hospital and Mubende RRH were added to the trial participating centres.
24/11/2022: Arua RRH, Koboko Hospital, Adjumani Hospital, Nebbi Hospital, Midigo HC4, Yumbe HC4, River Oli HC4, Moyo Hospital, Kisenyi HC4, Kawala HC4, Kasangati HC4, Wakiso HC4, Ndejje HC4, Namayumba HC4, Mukono General Hospital, Kawolo Hospital, Jinja RRH, Bugiri Hospital, Kamuli Hospital, Iganga Hospital, Mbale RRH, Luwero Hospital, Nakaseke Hospital, Kiboga Hospital, Masindi Hospital, Kiryandogo Hospital, Lira RRH, Soroti RRH, Gulu RRH, and Fortportal RRH were added to the trial participating centres.
14/11/2022: The recruitment start date was changed from 07/11/2022 to 13/11/2022.
06/09/2022: Trial's existence confirmed by the College of Medicine Research and Ethics Committee (COMREC) at the University of Malawi.
