Study of the Influence of Intraperitoneal Insufflation of CO2 by Laparoscopy on the Short-term Evolution of Premature Infants With Ulcerative Necrotizing Enterocolitis

Preterm Birth Clinical Trial

— NECO2  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05882448
• Other study ID #: APHP221170
• Status: Recruiting
• Phase: N/A
• Start date: February 22, 2024
• Est. completion date: September 2025

Study information

• Verified date: February 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Louise MONTALVA, Dr
• Phone: +33 1.71.73.89.97
• Email: louise.montalva[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: September 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Enterocolitis
• Enterocolitis, Necrotizing
• Premature Birth
• Preterm Birth

Intervention

Procedure:
• laparotomy
Exploratory and therapeutic laparotomy if necessary, in case of necrotic intestine requiring resection with anastomosis or stoma-type bowel diversion
• Laparoscopy
laparoscopy with insufflation of CO2 (placement of a 3mm trocar in the left hypochondrium and insufflation of a pneumoperitoneum (carbon dioxide, pressure: 6 mmHg, flow rate: 1.5 Liter/minute) for a duration of at least 5 minutes.

Locations

Country	Name	City	State
France	Hôpital Armand Trousseau Service de Chirurgie Pédiatrique et Néonatale	Paris
France	Hôpital Robert Debré Service de Chirurgie Pédiatrique	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	C reactive protein blood level	C reactive protein blood level	between Day 0 and Day 2 post surgery
Secondary	Postoperative biological inflammatory reaction	C reactive protein blood level	Day 7 post surgery
Secondary	Specific post-operative biological inflammatory reaction	Procalcitonin, Interleukin 6 and Tumor Necrosis Factor-alpha blood level	Day1, day 2, day 4 and day 7 post surgery
Secondary	Postoperative mortality	Death due to any postoperative cause	up to 3 months
Secondary	Postoperative intestinal morbidity: stoma rate	Stoma rate	up to 3 months
Secondary	Postoperative intestinal morbidity: Duration of parenteral nutrition	Duration of parenteral nutrition	up to 3 months
Secondary	Postoperative intestinal morbidity: Duration of hemodynamic support	Duration of hemodynamic support	up to 3 months
Secondary	Postoperative intestinal morbidity: Duration of invasive ventilation (HFO: High frequency oscillatory ventilation/VACI: Synchronized Intermittent Mandatory Ventilation)	Duration of invasive ventilation (HFO: High frequency oscillatory ventilation/VACI: Synchronized Intermittent Mandatory Ventilation)	up to 3 months
Secondary	Postoperative intestinal morbidity: Rate of intestinal stenosis post-ECUN	Rate of intestinal stenosis post-ECUN	up to 3 months
Secondary	Postoperative reoperation rate	Reoperation (laparotomy) and cause (post ECUN stenosis, stoma closure)	up to 3 months
Secondary	Length of hospitalization	Duration of hospitalization until return home	up to 3 months
Secondary	Medium-term postoperative neurological morbidity	Early postoperative neurological lesions observed on transfontanellar ultrasound and MRI at term corrected for 41 weeks of amenorrhea	up to 3 months
Secondary	Oxygen saturation (SaO2) (Tolerance of laparoscopy (Intraoperative cardio-respiratory))	Oxygen saturation (SaO2)	During Surgery
Secondary	Hypercapnia (pCO2) (Tolerance of laparoscopy (Intraoperative cardio-respiratory))	hypercapnia (pCO2)	During Surgery
Secondary	Blood pressure (BP) (Tolerance of laparoscopy (Intraoperative cardio-respiratory))	blood pressure (systolic and diastolic)	During Surgery
Secondary	Cerebral oxygenation (Near InfraRed Spectroscopy (NIRS)) (Tolerance of laparoscopy (Intraoperative cardio-respiratory))	cerebral oxygenation (Near InfraRed Spectroscopy (NIRS)) intraoperatively	During Surgery
Secondary	Presence of loco-regional lesions related to the insertion of the trocar (Tolerance of laparoscopy)	Presence of loco-regional lesions related to the insertion of the trocar	up to 3 months