Necrotizing EnterocolitisPhase 2RIC-NECNCT05279664
RIC-NEC Randomized Controlled Trial
A Phase 2 study of Necrotizing Enterocolitis, run by The Hospital for Sick Children at 4 sites in 2 countries.
Trial summary
Necrotizing enterocolitis (NEC) is a serious intestinal disease of preterm and term neonates which remains a major cause of intestinal failure, and an unsolved clinical challenge in pediatrics. Read more about this study
- Who is it for?
- Ages 0 weeks and older
- Conditions the study is for
- Necrotizing Enterocolitis
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 9 Feb 2023to 18 Mar 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 weeks and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All gestational age at birth.
- Current weight ≥600 g
- Confirmed diagnosis of "medical" NEC based on the joint opinion of two attending experts in the field (two neonatologists or one neonatologist and one pediatric surgeon).
- NEC diagnosis established within the previous 24 hours.
Who cannot join
- Indication for surgery in the joint opinion of the attending neonatologist and pediatric surgeon (i.e. surgical NEC). This diagnosis is based on the presence of pneumoperitoneum in the abdominal radiograph and/or failure of medical treatment for NEC
- Previous episodes of NEC
- Diagnosis of NEC established >24 hours ago
- Major congenital heart disease which needs surgical repair
- Antecedent limb ischemia/limb thrombotic events, occlusive arterial or venous thrombosis
- Associated gastrointestinal anomalies including gastroschisis or congenital diaphragmatic hernia.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Canada3 sites
Sunnybrook Health Sciences Center
Toronto, Ontario, M4Y 3M5
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
The Hospital for Sick Children
Toronto, Ontario, M5G1X8
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: RIC-NEC Phase II Feasibility Randomized Controlled Trial: Remote Ischemic Conditioning in Necrotizing Enterocolitis
Necrotizing enterocolitis (NEC) is a serious intestinal disease of preterm and term neonates which remains a major cause of intestinal failure, and an unsolved clinical challenge in pediatrics. While overall mortality of preterm infants continues to decrease due to improvements in general neonatal care, mortality caused by NEC remains high (up to 30-50%) and survivors suffer from reduced quality of life, and long-term disabilities such as debilitating complications of intestinal failure, poor growth and neurodevelopmental delay. Besides prevention, there have been hardly any innovations in the treatment of NEC which underwent trial evaluation.
NEC pathogenesis is multifactorial, but bowel ischemia is known to play an essential role in the development of NEC. Remote ischemic conditioning (RIC) is a therapeutic maneuver that involves brief cycles of non-lethal ischemia and reperfusion applied to a limb, which protects distant organs (such as the intestine) from ischemic damage. The investigators have shown that in preclinical models of NEC, RIC effectively reduces intestinal damage and prolongs survival. The investigators have also demonstrated the safety of RIC in preterm neonates with NEC. Before the investigators can evaluate the effectiveness of RIC in treating neonates with NEC in a Phase III randomized clinical trial (RCT), a Phase II Feasibility RCT must be conducted to evaluate issues related to the enrollment and randomization of neonates, masking of the RIC intervention, and measurement of clinical outcomes.
The investigators hypothesize that it is feasible to conduct a multicenter RCT to evaluate RIC during the management of neonates with medical NEC.
Read the detailed description
Background: Necrotizing enterocolitis (NEC) is a serious intestinal disease of preterm and term neonates which remains a major cause of intestinal failure, and an unsolved clinical challenge in pediatrics resulting in mortality rates as high as 50%, reduced quality of life and long-term disabilities such as short bowel syndrome, poor growth, and neurodevelopmental delay. Experimentally, the investigators have discovered that intestinal and brain damage, as well as mortality following NEC, can be avoided by remote ischemic conditioning (RIC) in the early stage of the disease. Remote ischemic conditioning is a therapeutic maneuver involving brief cycles of non-lethal ischemia and reperfusion applied to a limb that protects distant organs (such as the intestine) from sustained ischemic damage. In the clinical setting, the cycles of ischemia and reperfusion can be administered by inflation and deflation of a blood pressure cuff, similar to routine blood pressure measurements. The investigators have also demonstrated that this non-invasive, simple, and easy-to-use maneuver consisting of inflation/deflation of a blood pressure cuff on the upper arm is safe in preterm human neonates with NEC.
Hypothesis and Objectives: The investigators hypothesize that a masked multi-center randomized controlled trial of RIC in neonates with early-stage NEC is feasible.
Study design: This is a Phase II multicenter, masked, randomized controlled feasibility trial consisting of two arms: RIC (intervention) and no RIC (control).
Study population: Preterm neonates with clinical and radiological evidence of early-stage NEC and receiving medical treatment.
Sample size/power of primary endpoint: In the 12 international collaborating centers, the investigators expect to randomize, in 30 months, 78 patients with NEC receiving medical treatment (39 per arm) which represents 40% of approached eligible neonates.
- Conditions
- Necrotizing Enterocolitis
- Being tested
- Remote ischemic conditioning (RIC) + Standard of Care for NEC, Standard of Care for NEC
- Keywords
- remote ischemic conditioning, prematurity
- Medical subject headings
- Enterocolitis, Necrotizing, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote ischemic conditioning (RIC) + Standard of Care for NECOther
RIC will consist of 4 cycles of limb ischemia (5 min) followed by reperfusion (5 min), repeated on two consecutive days. An appropriately sized blood pressure cuff (covering 2/3 of the distance between the shoulder and the elbow) will be applied by a trained research fellow or nurse to an arm (or leg if the arm is not available because of medical reasons such as central line insertion). The systolic blood pressure will be measured before the first RIC cycle using a different cuff of same size connected to a monitor. During ischemia time, the cuff will be inflated to a pressure of 15 mmHg above the child's systolic pressure. Neonates in this arm will continue to receive standard of care for NEC.
Standard of Care for NECOther
Neonates in this arm (i.e. the control arm) will receive standard of care for NEC.
| Study group | Role | What they receive |
|---|---|---|
| Intervention (RIC + standard of care for NEC) | Experimental | Neonates randomized to the intervention arm will receive RIC and will continue to receive the standard of care for NEC. Receives: Other: Remote ischemic conditioning (RIC) + Standard of Care for NEC |
| Control (Standard of care for NEC) | Sham comparator | Neonates randomized to the control arm will receive the standard of care for NEC. The research fellow or nurse responsible for performing RIC will be performing sham inflation/deflation of the blood pressure cuff connected to a dummy arm to mimic the noise of the cuff for neonates in the control arm. Receives: Other: Standard of Care for NEC |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion (% total) of screened patients that are eligible for enrollment in the trial.
The investigators will determine the proportion (% total) of screened patients who meet the inclusion criteria and do not meet the exclusion criteria and are therefore eligible for enrollment in this study.
Measured: 24 hours
The proportion (% total) of eligible patients that give consent and are randomized.
The investigators will determine the proportion (% total) of eligible patients for whom informed consent from parents/caregivers can be obtained and randomization can be completed within 24 hours from confirmed diagnosis of medical NEC by a neonatologist and pediatric surgeon.
Measured: 24 hours
The proportion (% total) of randomized patients that receive allocated intervention.
The investigators will determine the proportion (% total) of patients randomized to each study arm who successfully receive the intervention corresponding to that arm: RIC or no RIC.
Measured: 72 hours
The proportion (% total) of randomized patients receiving masked allocated intervention.
The investigators will determine the proportion (% total) of randomized patients that receive the allocated intervention (RIC or no RIC) successfully masked from the circle of care as well as parents/caregivers.
Measured: 72 hours
The proportion (% total) of randomized patients assessed for NEC-related outcomes.
The investigators will determine the proportion (% total) of randomized patients that are successfully assessed for the NEC-related outcomes (please see secondary outcomes 6-13 below).
Measured: 3 months +/- 1 week
Secondary outcomes (8)
Number of patients surviving without the development of intestinal perforation, necrosis or stricture.
The investigators will determine the number of randomized patients who survive at 1 month and 3 months post-randomization without developing intestinal perforation, intestinal necrosis, or intestinal stricture.
Measured: 3 months +/- 1 week
Timing and cause of death
The time, and if possible, the cause of death will be recorded during the 90 days post-randomization considering whether it was possible to determine if death was related to complications of NEC or to a disease process in other systems including cardiac, neurological, respiratory, renal, metabolic.
Measured: 3 months +/- 1 week
Number, type and times of abdominal operations performed.
The number, time(s), and type(s) of abdominal operations (insertion of peritoneal drainage or laparotomy) performed during the 90 days post-randomization will be recorded.
Measured: 3 months +/- 1 week
Number of patients receiving parenteral nutrition
The number of patients receiving parenteral nutrition during the 90 days post-randomization will be recorded as a measure of intestinal function.
Measured: 3 months +/- 1 week
Number of patients developing severe neurological injury
Development of severe neurological injury will be assessed based on head ultrasound at 1-month and 3-months post-randomization and will be defined as the presence of intraventricular hemorrhage (IVH), ventricular enlargement, parenchymal echogenicity or periventricular leucomalacia (PVL).
Measured: 3 months +/- 1 week
Number of patients developing chronic lung disease (CLD)
Development of chronic lung disease (CLD) during the 90 days post-randomization will be defined as respiratory support given at 36 weeks' postmenstrual age or at discharge (if earlier than 36 weeks' postmenstrual age) to level 2 neonatal intensive care unit (NICU) and classified in different degrees of severity from mild to moderate to severe CLD according to the criteria published in the Canadian Neonatal Network (CNN) Annual Report (2019).
Measured: 3 months +/- 1 week
Number of patients developing severe retinopathy of prematurity (ROP)
During the 90 days post-randomization, the investigators will assess the development of Stage 3, 4 or 5 retinopathy of prematurity (ROP) as defined by the International Classification of ROP and/or those infants requiring treatment (laser or intraocular injection). ROP will be scored as the highest stage in either eye identified at any time.
Measured: 3 months +/- 1 week
Survey of stakeholders' satisfaction
Satisfaction of key trial stakeholders (parents and healthcare workers) with the recruitment process, delivery and masking of the intervention will be evaluated by questionnaires, using a scale of 0-4. Higher scores indicate greater satisfaction and lower scores indicate less satisfaction.
Measured: 1 month +/- 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2022
- Study start9 Feb 2023
- Primary completion20 Dec 2025
- Study completion18 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Necrotizing EnterocolitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The intervention used in this study is remote ischemic conditioning (RIC). Patients randomized to the intervention arm will receive RIC as well as the standard medical management for NEC. RIC will consist of 4 cycles of limb ischemia (5 minutes) followed by reperfusion (5 minutes), repeated on two consecutive days. An appropriately sized blood pressure cuff (covering 2/3 of the distance between the shoulder and the elbow) will be applied by a trained research fellow or nurse to an arm (or leg if the arm is not available because of medical reasons such as central line insertion). The systolic blood pressure will be measured before the first RIC cycle using a different cuff of the same size connected to a monitor. During ischemia time, the cuff will be inflated to a pressure of 15 mmHg above the child's systolic pressure.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Thrasher Research Fund, Mount Sinai Hospital, Canada, Sunnybrook Health Sciences Centre, McMaster Children's Hospital, Children's Hospital Medical Center, Cincinnati, Children's Hospital of Orange County, Karolinska University Hospital, Sophia Kindergeneeskunde, UCL Great Ormond Street Institute of Child Health, Hospital Universitario La Paz, University of Southampton, Xiamen Children's Hospital, Fujian of China, Shanghai Children's Hospital
- Responsible party
- Principal investigator, Agostino Pierro, The Hospital for Sick Children
- Investigators
- Agostino Pierro, OBE, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05279664
- Sponsor's protocol ID
- CTO 3802
- Acronym
- RIC-NEC
- Status last verified
- Jan 2026
- First submitted
- 11 Jan 2022
- Last updated
- 3 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Koike Y, Li B, Ganji N, Zhu H, Miyake H, Chen Y, Lee C, Janssen Lok M, Zozaya C, Lau E, Lee D, Chusilp S, Zhang Z, Yamoto M, Wu RY, Inoue M, Uchida K, Kusunoki M, Delgado-Olguin P, Mertens L, Daneman A, Eaton S, Sherman PM, Pierro A. Remote ischemic conditioning counteracts the intestinal damage of necrotizing enterocolitis by improving intestinal microcirculation. Nat Commun. 2020 Oct 2;11(1):4950. doi: 10.1038/s41467-020-18750-9.
PubMed 33009377Chen Y, Koike Y, Chi L, Ahmed A, Miyake H, Li B, Lee C, Delgado-Olguin P, Pierro A. Formula feeding and immature gut microcirculation promote intestinal hypoxia, leading to necrotizing enterocolitis. Dis Model Mech. 2019 Dec 9;12(12):dmm040998. doi: 10.1242/dmm.040998.
PubMed 31704804Chen Y, Chang KT, Lian DW, Lu H, Roy S, Laksmi NK, Low Y, Krishnaswamy G, Pierro A, Ong CC. The role of ischemia in necrotizing enterocolitis. J Pediatr Surg. 2016 Aug;51(8):1255-61. doi: 10.1016/j.jpedsurg.2015.12.015. Epub 2016 Jan 8.
PubMed 26850908Alganabi M, Lee C, Bindi E, Li B, Pierro A. Recent advances in understanding necrotizing enterocolitis. F1000Res. 2019 Jan 25;8:F1000 Faculty Rev-107. doi: 10.12688/f1000research.17228.1. eCollection 2019.
PubMed 30740215Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med. 2011 Jan 20;364(3):255-64. doi: 10.1056/NEJMra1005408. No abstract available.
PubMed 21247316Willan AR, Thabane L. Bayesian methods for pilot studies. Clin Trials. 2020 Aug;17(4):414-419. doi: 10.1177/1740774520914306. Epub 2020 Apr 16.
PubMed 32297539
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RIC-NEC Phase II Feasibility Randomized Controlled Trial: Remote Ischemic Conditioning in Necrotizing Enterocolitis
- ClinicalTrials.gov ID
- NCT05279664
- Acronym / sponsor ID
- RIC-NEC / CTO 3802
- Conditions
- Necrotizing Enterocolitis
- Keywords
- remote ischemic conditioning, prematurity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Thrasher Research Fund, Mount Sinai Hospital, Canada, Sunnybrook Health Sciences Centre, McMaster Children's Hospital, Children's Hospital Medical Center, Cincinnati, Children's Hospital of Orange County, Karolinska University Hospital, Sophia Kindergeneeskunde, UCL Great Ormond Street Institute of Child Health, Hospital Universitario La Paz, University of Southampton, Xiamen Children's Hospital, Fujian of China, Shanghai Children's Hospital
- Study start
- 9 Feb 2023 (actual)
- Primary completion
- 20 Dec 2025 (actual)
- Study completion
- 18 Mar 2026 (estimated)
- First posted
- 15 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Necrotizing enterocolitis (NEC) is a serious intestinal disease of preterm and term neonates which remains a major cause of intestinal failure, and an unsolved clinical challenge in pediatrics. While overall mortality of preterm infants continues to decrease due to improvements in general neonatal care, mortality caused by NEC remains high (up to 30-50%) and survivors suffer from reduced quality of life, and long-term disabilities such as debilitating complications of intestinal failure, poor growth and neurodevelopmental delay. Besides prevention, there have been hardly any innovations in the treatment of NEC which underwent trial evaluation.
NEC pathogenesis is multifactorial, but bowel ischemia is known to play an essential role in the development of NEC. Remote ischemic conditioning (RIC) is a therapeutic maneuver that involves brief cycles of non-lethal ischemia and reperfusion applied to a limb, which protects distant organs (such as the intestine) from ischemic damage. The investigators have shown that in preclinical models of NEC, RIC effectively reduces intestinal damage and prolongs survival. The investigators have also demonstrated the safety of RIC in preterm neonates with NEC. Before the investigators can evaluate the effectiveness of RIC in treating neonates with NEC in a Phase III randomized clinical trial (RCT), a Phase II Feasibility RCT must be conducted to evaluate issues related to the enrollment and randomization of neonates, masking of the RIC intervention, and measurement of clinical outcomes.
The investigators hypothesize that it is feasible to conduct a multicenter RCT to evaluate RIC during the management of neonates with medical NEC.
Detailed description
Background: Necrotizing enterocolitis (NEC) is a serious intestinal disease of preterm and term neonates which remains a major cause of intestinal failure, and an unsolved clinical challenge in pediatrics resulting in mortality rates as high as 50%, reduced quality of life and long-term disabilities such as short bowel syndrome, poor growth, and neurodevelopmental delay. Experimentally, the investigators have discovered that intestinal and brain damage, as well as mortality following NEC, can be avoided by remote ischemic conditioning (RIC) in the early stage of the disease. Remote ischemic conditioning is a therapeutic maneuver involving brief cycles of non-lethal ischemia and reperfusion applied to a limb that protects distant organs (such as the intestine) from sustained ischemic damage. In the clinical setting, the cycles of ischemia and reperfusion can be administered by inflation and deflation of a blood pressure cuff, similar to routine blood pressure measurements. The investigators have also demonstrated that this non-invasive, simple, and easy-to-use maneuver consisting of inflation/deflation of a blood pressure cuff on the upper arm is safe in preterm human neonates with NEC.
Hypothesis and Objectives: The investigators hypothesize that a masked multi-center randomized controlled trial of RIC in neonates with early-stage NEC is feasible.
Study design: This is a Phase II multicenter, masked, randomized controlled feasibility trial consisting of two arms: RIC (intervention) and no RIC (control).
Study population: Preterm neonates with clinical and radiological evidence of early-stage NEC and receiving medical treatment.
Sample size/power of primary endpoint: In the 12 international collaborating centers, the investigators expect to randomize, in 30 months, 78 patients with NEC receiving medical treatment (39 per arm) which represents 40% of approached eligible neonates.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- The intervention used in this study is remote ischemic conditioning (RIC). Patients randomized to the intervention arm will receive RIC as well as the standard medical management for NEC. RIC will consist of 4 cycles of limb ischemia (5 minutes) followed by reperfusion (5 minutes), repeated on two consecutive days. An appropriately sized blood pressure cuff (covering 2/3 of the distance between the shoulder and the elbow) will be applied by a trained research fellow or nurse to an arm (or leg if the arm is not available because of medical reasons such as central line insertion). The systolic blood pressure will be measured before the first RIC cycle using a different cuff of the same size connected to a monitor. During ischemia time, the cuff will be inflated to a pressure of 15 mmHg above the child's systolic pressure.
| Arm | Type | Receives |
|---|---|---|
| Intervention (RIC + standard of care for NEC) | Experimental | Other: Remote ischemic conditioning (RIC) + Standard of Care for NECNeonates randomized to the intervention arm will receive RIC and will continue to receive the standard of care for NEC. |
| Control (Standard of care for NEC) | Sham comparator | Other: Standard of Care for NECNeonates randomized to the control arm will receive the standard of care for NEC. The research fellow or nurse responsible for performing RIC will be performing sham inflation/deflation of the blood pressure cuff connected to a dummy arm to mimic the noise of the cuff for neonates in the control arm. |
Who may qualify
- Ages
- 0 weeks and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- All gestational age at birth.
- Current weight ≥600 g
- Confirmed diagnosis of "medical" NEC based on the joint opinion of two attending experts in the field (two neonatologists or one neonatologist and one pediatric surgeon).
- NEC diagnosis established within the previous 24 hours.
Key exclusion criteria (6 listed)
- Indication for surgery in the joint opinion of the attending neonatologist and pediatric surgeon (i.e. surgical NEC). This diagnosis is based on the presence of pneumoperitoneum in the abdominal radiograph and/or failure of medical treatment for NEC
- Previous episodes of NEC
- Diagnosis of NEC established >24 hours ago
- Major congenital heart disease which needs surgical repair
- Antecedent limb ischemia/limb thrombotic events, occlusive arterial or venous thrombosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Remote ischemic conditioning (RIC) + Standard of Care for NECRIC will consist of 4 cycles of limb ischemia (5 min) followed by reperfusion (5 min), repeated on two consecutive days. An appropriately sized blood pressure cuff (covering 2/3 of the distance between the shoulder and the elbow) will be applied by a trained research fellow or nurse to an arm (or leg if the arm is not available because of medical reasons such as central line insertion). The systolic blood pressure will be measured before the first RIC cycle using a different cuff of same size connected to a monitor. During ischemia time, the cuff will be inflated to a pressure of 15 mmHg above the child's systolic pressure. Neonates in this arm will continue to receive standard of care for NEC. | Other | Intervention (RIC + standard of care for NEC) |
| Standard of Care for NECNeonates in this arm (i.e. the control arm) will receive standard of care for NEC. | Other | Control (Standard of care for NEC) |
Primary outcome
The proportion (% total) of screened patients that are eligible for enrollment in the trial.
Time frame: 24 hours
The investigators will determine the proportion (% total) of screened patients who meet the inclusion criteria and do not meet the exclusion criteria and are therefore eligible for enrollment in this study.
The proportion (% total) of eligible patients that give consent and are randomized.
Time frame: 24 hours
The investigators will determine the proportion (% total) of eligible patients for whom informed consent from parents/caregivers can be obtained and randomization can be completed within 24 hours from confirmed diagnosis of medical NEC by a neonatologist and pediatric surgeon.
The proportion (% total) of randomized patients that receive allocated intervention.
Time frame: 72 hours
The investigators will determine the proportion (% total) of patients randomized to each study arm who successfully receive the intervention corresponding to that arm: RIC or no RIC.
The proportion (% total) of randomized patients receiving masked allocated intervention.
Time frame: 72 hours
The investigators will determine the proportion (% total) of randomized patients that receive the allocated intervention (RIC or no RIC) successfully masked from the circle of care as well as parents/caregivers.
The proportion (% total) of randomized patients assessed for NEC-related outcomes.
Time frame: 3 months +/- 1 week
The investigators will determine the proportion (% total) of randomized patients that are successfully assessed for the NEC-related outcomes (please see secondary outcomes 6-13 below).
8 secondary outcomes
Number of patients surviving without the development of intestinal perforation, necrosis or stricture.
Time frame: 3 months +/- 1 week
Timing and cause of death
Time frame: 3 months +/- 1 week
Number, type and times of abdominal operations performed.
Time frame: 3 months +/- 1 week
Number of patients receiving parenteral nutrition
Time frame: 3 months +/- 1 week
Number of patients developing severe neurological injury
Time frame: 3 months +/- 1 week
Number of patients developing chronic lung disease (CLD)
Time frame: 3 months +/- 1 week
Number of patients developing severe retinopathy of prematurity (ROP)
Time frame: 3 months +/- 1 week
Survey of stakeholders' satisfaction
Time frame: 1 month +/- 1 week
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2026.
- Background: PubMed 33009377Koike Y, Li B, Ganji N, Zhu H, Miyake H, Chen Y, Lee C, Janssen Lok M, Zozaya C, Lau E, Lee D, Chusilp S, Zhang Z, Yamoto M, Wu RY, Inoue M, Uchida K, Kusunoki M, Delgado-Olguin P, Mertens L, Daneman A, Eaton S, Sherman PM, Pierro A. Remote ischemic conditioning counteracts the intestinal damage of necrotizing enterocolitis by improving intestinal microcirculation. Nat Commun. 2020 Oct 2;11(1):4950. doi: 10.1038/s41467-020-18750-9.
- Background: PubMed 31704804Chen Y, Koike Y, Chi L, Ahmed A, Miyake H, Li B, Lee C, Delgado-Olguin P, Pierro A. Formula feeding and immature gut microcirculation promote intestinal hypoxia, leading to necrotizing enterocolitis. Dis Model Mech. 2019 Dec 9;12(12):dmm040998. doi: 10.1242/dmm.040998.
- Background: PubMed 26850908Chen Y, Chang KT, Lian DW, Lu H, Roy S, Laksmi NK, Low Y, Krishnaswamy G, Pierro A, Ong CC. The role of ischemia in necrotizing enterocolitis. J Pediatr Surg. 2016 Aug;51(8):1255-61. doi: 10.1016/j.jpedsurg.2015.12.015. Epub 2016 Jan 8.
- Background: PubMed 30740215Alganabi M, Lee C, Bindi E, Li B, Pierro A. Recent advances in understanding necrotizing enterocolitis. F1000Res. 2019 Jan 25;8:F1000 Faculty Rev-107. doi: 10.12688/f1000research.17228.1. eCollection 2019.
- Background: PubMed 21247316Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med. 2011 Jan 20;364(3):255-64. doi: 10.1056/NEJMra1005408. No abstract available.
- Background: PubMed 32297539Willan AR, Thabane L. Bayesian methods for pilot studies. Clin Trials. 2020 Aug;17(4):414-419. doi: 10.1177/1740774520914306. Epub 2020 Apr 16.
- Individual participant dataSharing planned: No
Related trials for Necrotizing Enterocolitis
Active, not recruitingObservational study
Early Predictors of Necrotizing Enterocolitis in Neonates
Necrotizing Enterocolitis
Recruiting
Effects of Enteral Feeding Regimens on NEC, Mortality, and Neurodevelopment in Very Preterm Infants
Very Preterm Infant, Necrotizing Enterocolitis (NEC)
RecruitingObservational study
The Correlation Between Red Cell Transfusion and Complications of Prematurity
Retinopathy of Prematurity (ROP), Bronchopulmonary Dysplasia (BPD)
RecruitingPhase 1
Gut Permeability and Microbiome in Preterm Infants
Prematurity Complications
Recruiting
WithHolding Enteral Feeds Around Blood Transfusion (International)
Necrotizing Enterocolitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Agostino Pierro, OBE, MD principal investigator
The Hospital for Sick Children
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study of Necrotizing Enterocolitis, run by The Hospital for Sick Children at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion (% total) of screened patients that are eligible for enrollment in the trial. (time frame: 24 hours). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05279664, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2026.