Clinical trial NCT03724214: Multi-Centre Gastroschisis Interventional Study Across Sub-Saharan Africa
Official title: Developing and Implementing an Interventional Bundle to Reduce Mortality From Gastroschisis in Low-Resource Settings
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Gastroschisis
Keywords: Gastroschisis
Sub-Saharan Africa
Low-resource settings
Low- and middle-income countries
Mortality
Outcomes
Implementation science
Intervention
Lead sponsor: King's College London
Sponsor class: OTHER
Collaborators: name: Korle-Bu Teaching Hospital, Accra, Ghana
name: Komfo Anokye Teaching Hospital
name: Ministry of Health, Ghana
name: University Teaching Hospital, Lusaka, Zambia
name: Arthur Davison Children's Hospital
name: Kamuzu Central Hospital
name: Muhimbili National Hospital, Dar es Salaam, Tanzania.
First posted: 2018-10-30
Enrollment: 235
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Pre and post study design. All patients presenting with simple gastroschisis during the pre-intervention phase will receive the current care provided by the study site. All patients with simple gastroschisis presenting to a study site following implementation will receive the interventional care bundle (if consent is provided).
Primary purpose: TREATMENT

Brief summary: This study is a multi-centre interventional study at seven tertiary paediatric surgery centres in Ghana, Zambia, Malawi and Tanzania aimed at reducing mortality from gastroschisis.

Detailed description: Background: Gastroschisis has a great disparity in outcomes globally with less than 4% mortality in high-income countries (HICs) and over 90% mortality in many tertiary paediatric surgery centres across sub-Saharan Africa (SSA), including the study centres. Low-technology, cost-effective, evidence-based interventions are available with the potential for improved outcomes in low-resource settings.

Aim: To develop, implement and prospectively evaluate an interventional care bundle to reduce mortality from gastroschisis in seven tertiary paediatric surgery centres across SSA.

Study Design: A hybrid type 2 effectiveness-implementation study design will be utilised, which focusses equally on the effectiveness of the intervention through analysing clinical outcomes and effectiveness of the implementation through analysis of service delivery and implementation outcomes.

Methods: Using current literature an evidence-based, low-technology interventional care bundle has been developed with both pre-hospital and in-hospital components. During 2018 a systematic review, qualitative study and Delphi process will provide further evidence in order to optimise the interventional bundle and implementation strategy for use in low-resource environments. The interventional care bundle has core components, which will remain consistent across the seven sites, and adaptable components, which will be determined through in-country co-development meetings with all relevant members of the multi-disciplinary team. Across the seven study sites it is estimated that 180-289 patients will be included in the study, which has the potential to determine a difference in pre- and post-intervention mortality between 10-15%.

Implementation will take place over a 4-week period at each of the study sites between April - December 2019. Pre- and post-interventional data will be collected on clinical, service delivery and implementation outcomes between September 2018 to October 2020 (2-years of patient recruitment at each site with a 30-day post primary intervention follow-up period). The primary clinical outcome will be all-cause, in-hospital mortality. Secondary outcomes include the occurrence of a major complication, length of hospital stay and time to full enteral feeds. Service delivery outcomes include time to hospital and primary intervention and adherence to the pre-hospital and in-hospital management protocols. Implementation outcomes will include acceptability, adoption, appropriateness, feasibility, fidelity, coverage, cost and sustainability.

Expected Results: Pre- and post-intervention clinical outcomes will be compared using Chi-squared analysis, unpaired t-test and/ or Mann-Whitney test. Time-series analysis will be undertaken using Statistical Process Control to identify significant trends and shifts in outcome overtime. Multivariate logistic regression analysis will be used to identify both clinical and implementation factors affecting outcome with adjustment for confounders. P\<0.05 will be deemed significant.

Outcome: This will be the first multi-centre interventional study to the investigator's knowledge aimed at reducing mortality from gastroschisis in low-resource settings. If successful, detailed evaluation of both the clinical and implementation components of the study will allow sustainability in the study sites and further scale-up.

Eligibility criteria: Inclusion Criteria:

* all neonates presenting primarily to the study centre with simple gastroschisis regardless of weight, gestational age or co-morbidities.

Exclusion Criteria:

* all neonates with 'complex gastroschisis' requiring surgical intervention for bowel necrosis, perforation, atresia or other reason.

Primary outcomes:
measure: All-cause, in-hospital mortality
timeFrame: Mortality whilst in hospital during primary admission, up to 30-days post-intervention or 30-days from admission for those not receiving an intervention and still in hospital.
Secondary outcomes:
measure: Percentage of patients experiencing a major complication within 30-days of primary intervention*
timeFrame: Within 30-days of primary intervention.
measure: Length of hospital stay amongst survivors
timeFrame: Up to a maximum of 30-days following primary intervention.
measure: Time to full enteral feeds
timeFrame: Up to a maximum of 30-days following primary intervention.
measure: Need for ventilation
timeFrame: Up to a maximum of 30-days following primary intervention.
measure: Duration of ventilation
timeFrame: Up to a maximum of 30-days following primary intervention.
Other outcomes:
measure: Service delivery outcomes: time from birth to arrival at the study centre
timeFrame: Time from birth to arrival at the study centre (typically less than 1 week)
measure: Service delivery outcomes: proportion of patients with clear plastic bowel coverage prior to arrival to the study centre
timeFrame: Birth to arrival at the study centre (typically less than 1 week)
measure: Service delivery outcomes: proportion of patients with intravenous fluids prior to arrival at hospital.
timeFrame: Birth to arrival at the study centre (typically less than 1 week)
measure: Service delivery outcomes: time from arrival to primary intervention
timeFrame: In-hospital, up to a maximum of 30-days from presentation to the study centre.
measure: Service delivery outcomes: position of multi-disciplinary team members involved during the initial resuscitation, primary intervention and defect closure
timeFrame: In hospital, within 30-days of presentation to the study centre
measure: Service delivery outcomes: proportion of patients receiving parenteral nutrition at some point during their hospital study
timeFrame: Up to a maximum of 30-days following primary intervention.
measure: Implementation outcome: acceptibility [assessed using the validated 'Acceptability of Intervention Measure' (AIM) Survey]
timeFrame: Survey to be administered at 2 time points: 1) during the 4th week of the implementation phase of the study (1 week) 2) on completion of the study (4 weeks).
measure: Implementation outcome: adoption
timeFrame: Survey to be administered at 2 time points: 1) during the 1st week of the implementation phase of the study (1 week) 2) on completion of the study (4 weeks).
measure: Implementation outcome: appropriateness [assessed using the validated 'Intervention Appropriateness Measure' (IAM) Survey].
timeFrame: Survey to be administered at 2 time points: 1) during the 4th week of the implementation phase of the study (1 week) 2) on completion of the study (4 weeks).
measure: Implementation outcome: feasibility [assessed using the validated 'Feasibility of Intervention Measure' (FIM) Survey].
timeFrame: Survey to be administered at 2 time points: 1) during the 4th week of the implementation phase of the study (1 week) 2) on completion of the study (4 weeks).
measure: Implementation outcome: fidelity.
timeFrame: 18-months (post-implementation phase of the study).
measure: Implementation outcome: fidelity.
timeFrame: 1 year (pre-intervention phase)
measure: Implementation outcome: fidelity.
timeFrame: 6 months (pre-intervention phase)
measure: Implementation outcome: fidelity.
timeFrame: 9 months (during the implementation phase of the study)
measure: Implementation outcome: fidelity.
timeFrame: 9 months (during the implementation phase of the study)
measure: Implementation outcome: fidelity.
timeFrame: 9 months (during the implementation phase of the study)
measure: Implementation outcome: fidelity.
timeFrame: 9 months (during the implementation phase of the study)
measure: Implementation outcome: fidelity.
timeFrame: 9 months (during the implementation phase of the study)
measure: Implementation outcome: coverage
timeFrame: 18-months (during the post-implementation phase of the study).
measure: Implementation outcome: cost
timeFrame: During the 2-years of data collection including pre- and post-implementation phases of the study.
measure: Implementation outcome: sustainability [assessed using the NHS Quality Improvement Sustainability Model]
timeFrame: At 3 specific time points in the study: 1) At the time of protocol development (3 months), 2) just prior to implementation of the interventional care bundle (1 week), 3) upon completion of the study (1 week).
Locations:
city: Montréal
country: Canada
facility: McGill University
city: Accra
country: Ghana
facility: Korle-Bu Teaching Hospital
city: Kumasi
country: Ghana
facility: Komfo Anokye Teaching Hospital
city: Tamale
country: Ghana
facility: Tamale Teaching Hospital
city: Lilongwe
country: Malawi
facility: Kamuzu Central Hospital
city: Dar Es Salaam
country: Tanzania
facility: Muhimbili National Hospital
city: London
country: United Kingdom
facility: King's Centre for Global Health and Health Partnerships, King's College London
city: Lusaka
country: Zambia
facility: University Teaching Hospital
city: Ndola
country: Zambia
facility: Arthur Davison Children's Hospital
Study officials:
affiliation: King's College London
name: Naomi J Wright, MBChB BSc MRCS DCH MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wright N, Abantanga F, Amoah M, Appeadu-Mensah W, Bokhary Z, Bvulani B, Davies J, Miti S, Nandi B, Nimako B, Poenaru D, Tabiri S, Yifieyeh A, Ade-Ajayi N, Sevdalis N, Leather A. Developing and implementing an interventional bundle to reduce mortality from gastroschisis in low-resource settings. Wellcome Open Res. 2019 Mar 8;4:46. doi: 10.12688/wellcomeopenres.15113.1. eCollection 2019.