Clinical trial NCT03205553: Direct Peritoneal Resuscitation in Gastroschisis
Official title: Direct Peritoneal Resuscitation in Gastroschisis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Gastroschisis
Keywords: Neonate
Lead sponsor: University of Arkansas
Sponsor class: OTHER
First posted: 2017-07-02
Enrollment: 3
Sex: ALL
Minimum age (years): 0
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective double-arm study designed to evaluate the tolerability of direct peritoneal resuscitation (DPR) in neonates with gastroschisis. The experimental arm (DPR group) will receive adjuvant DPR with standard treatment for gastroschisis (staged silo closure). The control arm (SoC group) will receive standard treatment for gastroschisis only. All subjects will be placed in a silo shortly after birth and within 2 hours of admission to the NICU and subsequently serially reduced in silo with umbilical tape until the bowel contents are at the level of fascia and deemed suitable for closure.
Primary purpose: OTHER

Brief summary: This is a prospective, double-arm study designed to evaluate the tolerability of direct peritoneal resuscitation (DPR) in neonates with gastroschisis. The experimental arm (DPR group) will receive adjuvant DPR with standard treatment for gastroschisis (staged silo closure). The control arm (SoC group) will receive standard treatment for gastroschisis without DPR.

The Research Team will prospectively enroll all neonates with the diagnosis of gastroschisis presenting to ACH within 12 hours after birth for whom consent is signed by the parent(s)/legally authorized representative (LAR). The Research Team anticipates enrolling 40 subjects at Arkansas Children's Hospital. All subjects that have their abdominal wall defect closed will be defined as having completed active participation in the study.

Detailed description: Gastroschisis is a clinical condition characterized by a defect in the normal development of the abdominal wall. The defect is present to the right of the umbilicus leading to in utero bowel evisceration and exposure to amniotic fluid. After birth and prior to operation, the usual treatment consists of covering the bowel with an impermeable plastic bag to prevent additional fluid losses and bowel desiccation. Subsequent operative intervention occurs either in the operating room or in the neonatal intensive care unit. Two surgical options include primary closure of the abdomen or placement of a silastic silo followed by subsequent closure several days later as a staged procedure. The main reason the abdominal wall is not closed initially is due to fear of abdominal compartment syndrome, a condition caused by high intra-abdominal pressures leading to respiratory and circulatory compromise. The key points of the initial surgery involve examining the intestine for any signs of atresia, bowel compromise, and either placement of the bowels back into the abdomen or a spring-loaded silo.

Arkansas Children's Hospital (ACH) has one of the highest rates of gastroschisis patients in the country and therefore has extensive experience managing these patients. It is not currently known why ACH has one of the highest rates of gastroschisis, but it has been postulated it may be due to some factor more common in low socioeconomic status population. ACH is the only pediatric hospital in the state of Arkansas. Quarterly, reviews of the Children's Hospital National Database (CHND) are performed to track the institutions progress in comparison to national trends. ACH's current surgical practice is to place nearly all patients in a silastic silo for staged reduction. Rarely are patients with gastroschisis treated with primary surgical closure at ACH. Serial reductions are performed and once the abdominal contents are at the level of the fascia the abdomen is closed in the operating room. Previous data indicates an average of five days from birth for final reduction and closure. After closure, there can be significant intestinal dysmotility with a prolonged ileus and a delayed return of bowel function. Generally, those with uncomplicated gastroschisis spend approximately 26 days in the neonatal intensive care unit before discharge home.

From historical CHND data, it is known that patients with simple gastroschisis have an average length of stay of 29 days, average of 5 days until abdominal wall closure, average of 7 days until start of enteral feeding after abdominal wall closure and average of 10 days until meeting 100 kcal per kg per day enteral feeds.

Direct Peritoneal Resuscitation The University of Louisville has been at the forefront of research for Direct Peritoneal Resuscitation (DPR). This technique uses clinically available peritoneal dialysis solution instilled into the abdomen with an initial bolus of 500 mL followed by a rate of 1.5 mL/kg/h in adults undergoing closure of the abdominal wall after traumatic injuries.

The aforementioned lab has also studied DPR in a rat model of hemorrhagic shock. The model has shown decreased mortality and increased intestinal and liver blood flow \[2-5\]. The group further investigated the use of DPR in a rat model of Necrotizing Enterocolitis (NEC) and discovered that 1.5% and 2.5% peritoneal dialysis solutions used as DPR improved intestinal blood flow, and with the 1.5% solution, there was less hyperglycemia than in the group treated with the 2.5% solution.

DPR has also been studied in the treatment of severely injured trauma patients and has shown a decrease in days until closure with improved outcomes. A randomized controlled study of 103 subjects requiring damage control surgery, i.e. open abdominal cavities, found that peritoneal resuscitation reduced the time to definitive abdominal closure, reduced intra-abdominal infections and reduced mortality.

Exposure of the abdominal viscera and its placement in a silo puts the neonate in a metabolically stressed state. Using DPR has been shown to counteract the systemic inflammatory response, leading to dilation of arterioles in the intestine resulting in reduced organ ischemia and cellular hypoxia.

Several case series have demonstrated safety of peritoneal dialysis in infants with recent abdominal surgery and intestinal perforation. In pediatric patients, peritoneal resuscitation has been used in two infants with perforated NEC who were too unstable to undergo laparotomy. Both survived and went on to undergo laparotomy.

The patient with gastroschisis is considered as an equivalent to the general surgery patient with the open abdomen and that adjunctive DPR treatment may be able to accelerate abdominal closure and improve outcomes.

It is hypothesized that the DPR group will have a more benign hospital course as measured by time to full enteral feeds of 100 kcal/kg/day. Time to abdominal wall closure, time on TPN, length of hospital stay and intestinal motility post-closure using bedside ultrasounds will also be assessed. Secondly, it is hypothesized that there will be no deleterious effects related to introducing the peritoneal dialysis solution into the silo.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Gastroschisis
* Male or Female, any ethnicity
* Neonates \[0-27 days as defined by the Age Classification in the ICH E-11\]

Exclusion Criteria:

* Primary gastroschisis repair
* Vanishing gastroschisis
* Encapsulating peritoneal sclerosis
* Infants \< 2 kg and \< 34 weeks gestation
* Infants \> 12 hours at enrollment
* Severe hypotension, defined as either:

  * Mean arterial blood pressure (MAP) \< gestational age in weeks, or
  * Systolic blood pressure (BP) \< 45 or diastolic BP \< 20
* Severe Hypertension defined as Systolic BP \> 90 or diastolic \> 60
* Culture-positive sepsis
* Known or strongly suspected inborn errors of metabolism
* Significant cardiac disorders, including cyanotic congenital heart disease, ductal-dependent congenital heart disease, and critical congenital heart disease (lesions requiring surgery or catheter-based intervention in the first year of life)
* Respiratory failure, defined as any requirement of positive pressure ventilation at the time of enrollment, or FiO2 \> 50%
* Any other condition, that, in the opinion of the investigator, might interfere with the safe conduct of the study or place the subject at increased risk
* Lactic acidosis with at least one or more of the following:

  * Characterized by increased blood lactate levels (\> 5 mmol/L) on two occasions at least 6 hours apart
  * Severe metabolic acidosis with an arterial pH ≤ 7.0
  * Bicarbonate \< 14 or CO2 \< 12
  * Base excess of \> -10 mEq/L
* Neonatal Acute Renal Failure, defined as serum creatinine \> 2.0 mg/dL with anuria in the first 12 hours of life
* Neonatal Acute Hepatic Failure, defined as INR \> 3
* Liver function test abnormalities defined as AST \> 200, ALT \> 200, GGT \> 100
* Electrolyte abnormalities, defined as:

  * Sodium \< 130 or \> 150 mEq/L
  * Potassium \< 3.0 or \> 6.5 mEq/L
* Hyperglycemia (\> 150 mg/dL) or hypoglycemia (\< 40 mg/dL)

Primary outcomes:
measure: Days to Full Enteral Feeds
timeFrame: Up to Hospital Discharge (average 30 days)
Secondary outcomes:
measure: Days to Abdominal Wall Closure
timeFrame: Up to 7 days
measure: Days on Total Parental Nutrition (TPN)
timeFrame: Until Day of Discharge, an average of 29 days
measure: Days to Intestinal Motility
timeFrame: Up to 3 weeks post-closure
measure: Number of Days in the Hospital
timeFrame: Until Day of Discharge, an average of 40 days
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Childrens Hospital
state: Arkansas
Study officials:
affiliation: University of Arkansas for Medical Sciences (UAMS)
name: Patrick C Bonasso, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Arkansas Children's Hospital Research Institute
name: Samuel Smith, MD
role: PRINCIPAL_INVESTIGATOR
References: