Multi-Centre Gastroschisis Interventional Study Across Sub-Saharan Africa

Study Overview
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Brief Summary
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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
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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.

Official Title
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Developing and Implementing an Interventional Bundle to Reduce Mortality From Gastroschisis in Low-Resource Settings

Conditions
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Gastroschisis

Intervention / Treatment
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* Combination Product: Pre-hospital interventional care bundle
* Combination Product: In-hospital interventional care bundle


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional 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).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Pre-intervention<br>Patients presenting with simple gastroschisis during the pre-intervention phase will receive the current care provided by the study sites (no intervention). | |
| Active Comparator: Post-intervention<br>Patients presenting with simple gastroschisis during the post-implementation phase will receive the interventional care bundle if consent for participation is provided. | Combination Product: Pre-hospital interventional care bundle<br>* The interventional care bundle will include pre-hospital and in-hospital components and core and adaptable components. All seven centres will implement the core pre-hospital and in-hospital components. Implementation of the adaptable components will be decided by the local team to optimise the interventional care bundle to the local environment. Pre-hospital core components: 1) covering the bowel in clear plastic, 2) administering intravenous fluids, 3) keeping the neonate warm, 4) transferring to a study centre as soon as possible. This will be implemented as a pre-hospital gastroschisis care protocol to district and secondary level hospitals who refer patients with gastroschisis to the study centres. Pre-hospital adaptable components: 1) the strategy for disseminating the pre-hospital gastroschisis care protocol.<br>Combination Product: In-hospital interventional care bundle<br>* In-hospital core components: 1) use of a standardised care protocol, 2) neonatal resuscitation and ward care including intravenous access, intravenous fluids, maintenance of normothermia, appropriate antibiotics, regular monitoring and infection control, 3) gastroschisis reduction and sutureless closure using a preformed silo and avoidance of neonatal anaesthesia and surgery, 4) early establishment of breastfeeding and an enhanced enteral feeding programme. In-hospital adaptable components: 1) administration of parenteral nutrition for neonates who have survived for 1-week in hospital, 2) maternal involvement in monitoring and basic management, 3) management of neonates with gastroschisis on the neonatal intensive care unit if available.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause, in-hospital mortality | Percentage of patients with gastroschisis dying in hospital during their primary admission. | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients experiencing a major complication within 30-days of primary intervention* | Major complications are secondary bowel ischaemia, necrosis or perforation requiring resection**, abdominal compartment syndrome*** or need for further unplanned surgical intervention. *Defined as the first bowel intervention the neonate received including silo application or primary closure. **Defined as bowel necrosis or perforation that was not present prior to primary intervention and hence occurred after primary intervention. ***Defined as respiratory insufficiency secondary to compromised tidal volumes, decreased urine output by falling renal perfusion (<1ml/kg/hr) and any other organ dysfunction caused by increased intra-abdominal pressure (based on clinical judgement - the pressure does not have to be measured to fulfil the criteria). | Within 30-days of primary intervention. | 
| Length of hospital stay amongst survivors | In days. | Up to a maximum of 30-days following primary intervention. | 
| Time to full enteral feeds | In days | Up to a maximum of 30-days following primary intervention. | 
| Need for ventilation | Yes/ no. This does not include ventilation given during anaesthesia for intervention(s). | Up to a maximum of 30-days following primary intervention. | 
| Duration of ventilation | IN days. All ventilation types included. | Up to a maximum of 30-days following primary intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastroschisis, Sub-Saharan Africa, Low-resource settings, Low- and middle-income countries, Mortality, Outcomes, Implementation science, Intervention