Clinical Trial for Valuation of the Effectiveness of Lactoferrine in the Prevention of Sepsis in New Premature Born. Bimonitorization of the Antinflammatory Mechanisms, Antioxidants and the Intestinal Microbiote. (LACTOPREM)

To evaluate the efficacy of enteral administration of bovine lactoferrin (bLf) in the reduction of probable late sepsis or microbiologically proven in preterm infants with birth weight ≤ 1500 gr and / or gestational age ≤ 32 weeks.

Study Overview

• Status: Unknown
• Conditions: SEPSIS SYNDROME
• Intervention / Treatment: Dietary supplement: Enteral administration of bovine lactoferrin (bLf); Other: Enteral administration of placebo

Detailed Description

To date there are no published clinical data that jointly assess the impact of direct Lf supplementation on oxidative status, on biomarkers of systemic inflammation and on the microbiota of premature infants with or without sepsis. Clarification of these additional questions is essential for a better understanding of the benefits and implications of enteral administration of Lf in preterm infants. The enteral administration of lactoferrin reduces the incidence of late sepsis in preterm infants of very low birth weight (BMPN). Enteral supplementation with lactoferrin in NBWNS can have a beneficial effect on the systemic oxidative and inflammatory state, and may contribute to the creation of a healthy faecal microbiota.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Antonio Miguel Luque Pineda; Phone Number: 00 34 957 011 040; Email: uicec@imibic.org
• Study Contact Backup: Name: María Dolores Ordoñez, MD; Email: mdordonezdiaz@gmail.com

Study Locations

• Spain
  • Córdoba, Spain, 14004
    • Recruiting
    • Hosìtal Universitario Reina Sofia
    • Contact: María Dolores Ordoñez, MD; Email: mdordonezdiaz@gmail.com
    • Principal Investigator: María Dolores Ordoñez, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 7 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Both groups will include male or female children born preterm with birth weight ≤ 1500 g and / or EG ≤ 32 weeks. All tutors of patients, must sign the informed consent.

Exclusion Criteria:

• In both groups those subjects who do not meet the age and weight established at birth, have> 72 hours of life at the time of inclusion, who do not sign informed consent or who have the following morbidities will be discarded: 1) Early sepsis or vertical; 2) Gastrointestinal congenital anomalies; 3) Chromosomopathies; 4) Congenital anomalies and / or genetic diseases without survival expectations; 5) Severe perinatal hypoxia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm; The nutritional supplement used will be bovine lactoferrin, a product marketed according to the regulations of the European Union, and approved by the European Food Safety Agency (EFSA) in 2012, and by the American Agency for Food and Drug Administration ( FDA) in 2013. It will be acquired after purchase from Dicofarm® (Rome, Italy). The Hospital Pharmacy Service will provide the established dose of lactoferrin, according to the administration schedule of 150 mg / kg / day (maximum 300 mg / day). The treatments will be administered in liquid form, in the least amount possible. The administration of lactoferrin will be carried out enterally, orally or by nasogastric tube. The intervention will be done in the first 72 hours of life, once a day, and for 4 weeks, extending to 6 weeks in the NB with EG ≤ 28 weeks and / or birth weight ≤ 1000 gr, or until discharge if this happens before.	Dietary supplement: Enteral administration of bovine lactoferrin (bLf); The pharmacy service of the hospital will provide the established dose of lactoferrin, according to the regimen of administration of 150 mg / kg / day (maximum 300 mg / day), as well as that of placebo. Both treatments will be administered in liquid form, in the least amount possible. Both the administration of lactoferrin and placebo will be carried out enterally, orally or by nasogastric tube. The intervention will be done in the first 72 hours of life, once a day, and for 4 weeks, extending to 6 weeks in the newborns with EG ≤ 28 weeks and / or birth weight ≤ 1000 gr, or until discharge if this happens before.
Placebo Comparator: Control Arm; Placebo with similar visual and taste characteristics to the nutritional supplement of bovine lactoferrin. It will be administered in liquid form, in the least amount possible. The administration of placebo will be carried out enterally, orally or by nasogastric tube. The intervention will be done in the first 72 hours of life, once a day, and for 4 weeks, extending to 6 weeks in the NB with EG ≤ 28 weeks and / or birth weight ≤ 1000 gr, or until discharge if this happens before.	Other: Enteral administration of placebo; Enteral administration of placebo with similar visual and gustatory characteristics in the first 72 hours of life, and for 4 weeks (6 weeks in the RN ≤ 1000 gr and / or EG ≤ 28 weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of proven and probable late sepsis	To evaluate the efficacy of enteral administration of bovine lactoferrin (bLf) in the reduction of probable late sepsis or microbiologically proven in preterm infants with birth weight ≤ 1500 gr and / or gestational age ≤ 32 weeks.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perinatal history and demographic characteristics	Description of the perinatal history and demographic characteristics in the subjects of two intervention groups (lactoferrin vs placebo).	At baseline.
Morbidities	Assess the possible differences between the two groups with respect to the following morbidities: Global mortality and / or attributable to late sepsis before hospital discharge; Necrotizing enterocolitis; Retinopathy of prematurity; Bronchopulmonary dysplasia; Cerebral hemorrhage and periventricular leukomalacia; Hospital stay; Seriousness of late sepsis; Food tolerance	From 72 hours until 4 weeks after birth
Adverse effects	Evaluation of the safety of the administration of lactoferrin by monitoring possible adverse effects.	From 72 hours until 4 weeks after birth and in every visit (months 3, 6, 12 y 24 after hospital discharge).
Parameters of inflammation and oxidative stress	Biomonitoring parameters of inflammation and oxidative stress in both groups, comparing possible differences.	0-24 hours of life, 7-10 days, 14-17 days of life, and one last extraction at the end of treatment, at 28-31 days
Intestinal microbiota	Study and compare the composition of the intestinal microbiota between both groups. Its modification will be assessed before and after treatment, and the implication of its distortion in late sepsis.	Before and after treatment
Subgroups evaluation	Analyze the results based on subgroups established by gestational age, birth weight, type of feeding and etiology of sepsis.	At the end of the trial.
Anthropometric parameters and neurodevelopment	Evaluation of anthropometric parameters and neurodevelopment at 2 years of corrected age.	At 2 years of corrected age

Collaborators and Investigators

• Sponsor: Maimónides Biomedical Research Institute of Córdoba
• Investigators: Principal Investigator: María Dolores Ordoñez, Maimónides Biomedical Research Institute of Córdoba

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2017
• Primary Completion (Anticipated): March 1, 2020
• Study Completion (Anticipated): March 1, 2020

Study Registration Dates

• First Submitted: March 14, 2018
• First Submitted That Met QC Criteria: March 14, 2018
• First Posted (Actual): March 21, 2018

Study Record Updates

• Last Update Posted (Actual): November 14, 2019
• Last Update Submitted That Met QC Criteria: November 11, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: bovine lactoferrin; late sepsis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Shock; Sepsis; Toxemia; Systemic Inflammatory Response Syndrome; Anti-Infective Agents; Lactoferrin
• Other Study ID Numbers: FCO-LAC-2016-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The individual participant data will be available.

Individual parcicipant data that underlie the results reportes in this article, after deidenttification (text, tables, figures and appendices)

The other documents that will be available: study protocol, Statistical Analysis Plan, Informed Consent Form.

With whom? Researchers who provide a methodologically sound proposal.

For what types of analyses? for individual participant data meta-analysis.

• IPD Sharing Time Frame: Open under request.
• IPD Sharing Access Criteria: To obtain the data, a proposal must be sent to uicec@imibic.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No