Clinical trial NCT05882448: Study of the Influence of Intraperitoneal Insufflation of CO2 by Laparoscopy on the Short-term Evolution of Premature Infants With Ulcerative Necrotizing Enterocolitis
Official title: Study of the Influence of Intraperitoneal Insufflation of Carbon Dioxide (CO2) by Laparoscopy on the Short-term Evolution of Premature Infants With Ulcerative Necrotizing Enterocolitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Preterm Birth
Enterocolitis, Necrotizing
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-05-31
Enrollment: 54
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: parallel assignment
Primary purpose: TREATMENT

Brief summary: Ulcerative-necrotizing enterocolitis (ECUN) is an infectious and inflammatory disease of the digestive tract, which can lead to intestinal necrosis or perforation.

This severe pathology of the newborn , often premature, requires urgent medical and surgical treatment in 25 to 50% of cases. The morbidity is high, both digestive and neurological. ECUN can lead to complications at short-term (death, intestinal stenosis) and at long-term (neuro-cognitive disorders). The challenge of preserving the neurological development is a major issue. It involves control of inflammation. This inflammation causes neurological lesions and is responsible for a disorder of the long-term neurocognitive development.

At Robert-Debré and Trousseau, the management of newborns with ECUN is focused on the control of this inflammation. A laparoscopy is performed first. The carbon dioxide (CO2) insufflated into the abdomen during a laparoscopy is thought to have an anti-inflammatory effect according to several experimental and clinical studies. A preliminary retrospective study at Robert-Debré showed a decrease in postoperative inflammation (decrease in C reactive protein at Day2 and Day 7 post-op) as well as a decrease in morbimortality (decrease in the rate of stoma and reoperation) in children who had a laparoscopic first operation compared to those who had a laparotomy alone. However, in many hospitals, laparotomy alone is currently the only surgical option.

This preliminary study may demonstrate that laparoscopy decreases early morbidity and mortality in children with ECUN through reduced inflammation, as reflected by postoperative C reactive protein.

Detailed description: NECO2 is a pilot trial, evaluating the intermediate effectiveness to short/medium term of laparoscopy on the inflammatory reaction of premature newborns with complicated ECUN, requiring surgical treatment.

This is a multicenter randomized controlled trial in single blind, in two parallel arms, in ratio 1:1, of superiority.

This trial compares laparoscopy plus laparotomy versus laparotomy alone.

Children will be randomized into 2 groups:

* Laparoscopy + laparotomy group
* Laparotomy group

The main objective is to evaluate the inflammatory response Day 2 postoperative in preterm infants with ECUN who have undergone surgery.

The main criterion is the evolution of the blood C reactive protein level between Day 0 and Day 2 postoperatively.

The secondary objectives are:To evaluate in premature babies with ECUN who have had a surgical intervention (laparoscopy + laparotomy or laparotomy alone):

A.The postoperative biological inflammatory response at Day 7 B.Post-operative biological inflammatory response from Day 0 to Day 7 C.Post-operative mortality D.Post-operative bowel morbidity E.Post-operative re-intervention rate F.Length of hospital stay G.Post-operative neurological morbidity, medium term (corrected term 41 SA)

* To evaluate the tolerance of laparoscopy :

H.Intraoperative cardiorespiratory I.Loco-regional lesions linked to the insertion of the trocar

Secondary endpoints:

A. C reactive protein blood level at Day 7 B. Blood levels of Procalcitonin, Interleukin 6 and Tumor Necrosis Factor-alpha at Day 1, Day 2, Day 4, Day 7 C. Postoperative death from any cause D. Stoma rate, duration of parenteral nutrition, duration of hemodynamic support, duration of invasive ventilation (High frequency oscillatory ventilation/Synchronized Intermittent Mandatory Ventilation), Post-ECUN intestinal stenosis rate E. Re-intervention (laparotomy) and cause (post-ECUN stenosis, stoma closure) F. Length of hospital stay until return home G. Early postoperative neurological lesions observed on transfontanellar ultrasound and MRI at the corrected term of 41 weeks of amenorrhea, H. Oxygen saturation (SaO2), hypercapnia (pCO2) blood pressure (BP), cerebral oxygenation (Near InfraRed Spectroscopy (NIRS)) intraoperatively I. Intraoperative clinical monitoring: exploration of adjacent organs. Post-operative clinical monitoring: digestive signs monitoring of wounds until discharge.

Group 1: laparotomy only Group 2: laparotomy and laparoscopy

Eligibility criteria: Inclusion Criteria:

* Premature newborn (term of birth: \<37 weeks of amenorrhea)
* Diagnosis of ECUN by the surgeon (distension abdominal +/- rectal bleeding +/- green gastric residue, increased biological inflammatory syndrome, + pneumatosis on abdominal radiography)
* Hospitalized and complicated ECUN: presenting either a pneumoperitoneum on abdominal X-ray or a absence of clinical and biological improvement after 48 hours of maximum well-conducted medical treatment (IV antibiotic therapy and digestive rest).
* Hospitalized in the 2 participating centers
* Of which the 2 holders of parental authority have been informed and have signed the consent form
* Having social security coverage (social security or CMU)

Exclusion Criteria:

* Instability contraindicating movement to the operating room or contraindicating CO2 insufflation
* Diagnosis of isolated perforation of the small intestine (radiography:

pneumoperitoneum without pneumatosis)

Primary outcomes:
measure: C reactive protein blood level
timeFrame: between Day 0 and Day 2 post surgery
Secondary outcomes:
measure: Postoperative biological inflammatory reaction
timeFrame: Day 7 post surgery
measure: Specific post-operative biological inflammatory reaction
timeFrame: Day1, day 2, day 4 and day 7 post surgery
measure: Postoperative mortality
timeFrame: up to 3 months
measure: Postoperative intestinal morbidity: stoma rate
timeFrame: up to 3 months
measure: Postoperative intestinal morbidity: Duration of parenteral nutrition
timeFrame: up to 3 months
measure: Postoperative intestinal morbidity: Duration of hemodynamic support
timeFrame: up to 3 months
measure: Postoperative intestinal morbidity: Duration of invasive ventilation (HFO: High frequency oscillatory ventilation/VACI: Synchronized Intermittent Mandatory Ventilation)
timeFrame: up to 3 months
measure: Postoperative intestinal morbidity: Rate of intestinal stenosis post-ECUN
timeFrame: up to 3 months
measure: Postoperative reoperation rate
timeFrame: up to 3 months
measure: Length of hospitalization
timeFrame: up to 3 months
measure: Medium-term postoperative neurological morbidity
timeFrame: up to 3 months
measure: Oxygen saturation (SaO2) (Tolerance of laparoscopy (Intraoperative cardio-respiratory))
timeFrame: During Surgery
measure: Hypercapnia (pCO2) (Tolerance of laparoscopy (Intraoperative cardio-respiratory))
timeFrame: During Surgery
measure: Blood pressure (BP) (Tolerance of laparoscopy (Intraoperative cardio-respiratory))
timeFrame: During Surgery
measure: Cerebral oxygenation (Near InfraRed Spectroscopy (NIRS)) (Tolerance of laparoscopy (Intraoperative cardio-respiratory))
timeFrame: During Surgery
measure: Presence of loco-regional lesions related to the insertion of the trocar (Tolerance of laparoscopy)
timeFrame: up to 3 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Armand Trousseau Service de Chirurgie Pédiatrique et Néonatale
city: Paris
country: France
facility: Hôpital Robert Debré Service de Chirurgie Pédiatrique
Study officials:
References: