Clinical trial NCT02907632: Methoclopramide for Gastroesophageal Reflux in Premature Infants
Official title: Use of Metoclopramide for the Prevention of Gastroesophageal Reflux in Premature Infants Followed in an Outpatient Kangaroo Mother Care Clinic Before 40 Weeks of Gestational Age: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Gastroesophageal Reflux
Keywords: Metoclopramide
Pro kinetic
Gastroesophageal Reflux
Premature Infant
Low Birth Weight
Kangaroo Mother Care Method
Lead sponsor: Kangaroo Foundation
Sponsor class: OTHER
Collaborators: name: Hospital Universitario San Ignacio
name: Pontificia Universidad Javeriana
First posted: 2016-09-20
Enrollment: 490
Sex: ALL
Minimum age (years): 1
Maximum age (years): 100
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Gastroesophageal Reflux (GER) is a condition that affects the majority of premature infants that are followed at the Kangaroo Mother Care Program (ambulatory program for preterm infants discharged with their mothers in continuous skin to skin contact and strict outpatient follow up). For over 20 years, the use of Metoclopramide has been systematic among all preterm infants according to the protocols of the Kangaroo Mother Care (KMC) Program . The aim of this clinical trial is to evaluate the effectiveness and security of metoclopramide to lessen the symptoms of GRE in premature infants that are followed and treated in the Ambulatory KMC Program before 40 weeks of gestational age. Design: Randomized, double blind trial, controlled with placebo. Eligible Population: Premature infants that are followed and treated in the Ambulatory Kangaroo Mother Care Program at Hospital Universitario San Ignacio before 40 weeks of gestational age, which systematically receive: metoclopramide 0.2 mg per kg, every 8 hours, 15 minutes before every feeding up to 40 weeks of gestational age, between January 01 2017 and December 31 2017.Outcomes: Incidence of regurgitation episodes reported by the parents of the infants, episodes of apnea, bronchoaspiration, postprandial irritability, the infant rejects feeding, alteration in the postprandial posture and the frequency and severity of adverse effects associated with the use of Metoclopramide such as extrapyramidal symptoms and sedation. In the case of continuous variables, the mean and median will be compared according to the distribution and for nominal variables, a chi squared test or fisher test will be carried out.

Duration: 12 months. Ethical Aspects: Experiment with minimum mayor risk. Informed consent will be requested to parents. An independent committee from the work group will be in charge of carrying out the follow-up of the safety and progression of the study. A methodological expert, a thematic expert, a statistician and an expert in bioethics will constitute the committee.

Financial Disclosure: The study will be funded through the Kangaroo Foundation with the collaboration of the " Hospital Universitario San Ignacio", Bogotá, Colombia.

Detailed description: Justification: Gastroesophageal Reflux (GER) is a condition that affects the majority of premature infants that are followed at the Kangaroo Mother Care Program. The incidence of GRE in premature infants can oscillate between 22 and 85% depending on the criteria used to diagnose GER, which can vary among healthcare professionals.

For over 20 years, the use of metoclopramide has been systematic among all preterm infants according to the protocols of the Kangaroo Mother Care (KMC) Program. These protocols were established according to the recommendations emitted by the Cochrane Collaboration in 2006, nevertheless according to new studies published in the last years, the controversial evidence referring the use of metoclopramide given the eventual possibility of adverse effects and the lack of evidence in premature infants, it is necessary to evaluate whether it is pertinent to continue the use of metoclopramide in premature infants and the risk of adverse effects.

Objective: To evaluate the effectiveness and security of metoclopramide to lessen the symptoms of GRE in premature infants that are followed and treated in the Ambulatory KMC Program before 40 weeks of gestational age.

Design: Randomized, double blind trial, controlled with placebo. Eligible Population: Premature infants that are followed and treated in the Ambulatory KMC Program at Hospital Universitario San Ignacio before 40 weeks of gestational age, which systematically receive: metoclopramide 0.2 mg per kg, every 8 hours, 15 minutes before every feeding up to 40 weeks of gestational age, between April 1 2017 and January 31 2019. Intervention: Blind and randomized allocation to the experimental treatment (metoclopramide 0.2 mg per kg, every 8 hours, 15 minutes before every feeding up to 40 weeks of gestational age) or placebo.

Outcomes: Incidence of regurgitation episodes reported by the parents of the infants, episodes of apnea, bronchoaspiration, postprandial irritability, the infant rejects feeding, alteration in the postprandial posture and the frequency and severity of adverse effects associated with the use of metoclopramide such as extrapyramidal symptoms and sedation. In the case of continuous variables, the mean and median will be compared according to the distribution and for nominal variables, a chi squared test or fisher test will be carried out.Intervention: Blind and randomized allocation to the experimental treatment (metoclopramide 0.2 mg per kg, every 8 hours, 15 minutes before every feeding up to 40 weeks of gestational age) or placebo.

Expected Results: Reliable information regarding the use of metoclopramide in premature infants for the prevention of regurgitation episodes associated to apnea, cyanosis, irritability, rejection of feeding efforts, bronchoaspiration and poor weight gain as well as adverse effects.

Duration: 12 months. Ethical Aspects: Experiment with minimum mayor risk. Informed consent will be requested to parents. An independent committee from the work group will be in charge of carrying out the follow-up of the safety and progression of the study. A methodological expert, a thematic expert, a statistician and an expert in bioethics will constitute the committee.

Financial Disclosure: The study will be funded through the Kangaroo Foundation with the collaboration of the " Hospital Universitario San Ignacio", Bogota, Colombia.

Eligibility criteria: Inclusion Criteria:

Preterm infants followed at ambulatory Kangaroo Mother Care Program(KMCP) in Hospital San Ignacio, Bogotá, Colombia.

Exclusion Criteria:

Hipoxic- Ischemic Encephalopathy. Periventricular Leukomalacia (PVL). Intraventricular hemorrhage grade 3 or 4. Severe dystonia Seizures. Liver failure. Renal insufficiency. Previous adverse events with the use of Metoclopramide. Parents don´t agree participation.

Primary outcomes:
measure: Incidence of regurgitation episodes
timeFrame: Until 40 weeks Post Menstrual Age
Secondary outcomes:
measure: Episodes of apnea
timeFrame: Until 40 weeks Post Menstrual Age
measure: Bronchoaspiration
timeFrame: Until 40 weeks Post Menstrual Age
measure: Postprandial irritability
timeFrame: Until 40 weeks Post Menstrual Age
measure: The infant rejects feeding
timeFrame: Until 40 weeks Post Menstrual Age
measure: Alteration in the postprandial posture
timeFrame: Until 40 weeks Post Menstrual Age
Other outcomes:
measure: extrapyramidal symptoms
timeFrame: Until 40 weeks Post Menstrual Age
Locations:
city: Bogotá
country: Colombia
facility: Nathalie Charpak
state: Cundinamarca
Study officials:
affiliation: Kangaroo Foundation Director
name: Nathalie Charpak, Dr.
role: STUDY_DIRECTOR
References:
citation: Hibbs AM, Lorch SA. Metoclopramide for the treatment of gastroesophageal reflux disease in infants: a systematic review. Pediatrics. 2006 Aug;118(2):746-52. doi: 10.1542/peds.2005-2664.
citation: Tighe MP, Afzal NA, Bevan A, Beattie RM. Current pharmacological management of gastro-esophageal reflux in children: an evidence-based systematic review. Paediatr Drugs. 2009;11(3):185-202. doi: 10.2165/00148581-200911030-00004.
citation: Montealegre-Pomar ADP, Charpak N. Randomized Clinical Trial of Metoclopramide as Prophylaxis of Gastroesophageal Reflux Disease in Preterm Infants. Paediatr Drugs. 2021 Nov;23(6):591-599. doi: 10.1007/s40272-021-00475-x. Epub 2021 Oct 25.