Effectiveness of Oral Immunotherapy Among Preterm Babies

• ClinicalTrials.gov Identifier: NCT03633500
• Recruitment Status: Completed
• First Posted: August 16, 2018
• Last Update Posted: July 12, 2019
• Sponsor: Al Adan Hospital Kuwait
• Information provided by (Responsible Party): Shiney Easo, Al Adan Hospital Kuwait

Study Description

Brief Summary:

The aim of the study is to assess the effectiveness of OIT with colostrum on the feeding behavior and Clinical Outcome of Late-onset sepsis and Necrotizing enterocolitis

Condition or disease	Intervention/treatment	Phase
Feeding Behavior; Late-Onset Neonatal Sepsis	Other: Sterile water; Biological: Breastmilk	Not Applicable

Detailed Description:

A randomized placebo-controlled double-blinded study in preterm infants < 32+6 weeks' gestation or Birth weight < 1500 g who are admitted to NICU.

Exclusion criteria include infants with congenital anomalies, out born infants, infants of single mothers with unknown partners (mother is separated from preterm infants based on the state law) and infants admitted beyond 48 hours of age, confirmed immunodeficiency disorder, Inborn Error of Metabolism, parental refusal to participate. The infants who have overt bleeding, thrombocytopenia < 50,000/mm3 or are critically ill requiring multiple inotropes in high doses, on High frequency ventilation and inhaled nitric oxide and infants with congenital surgical abdomen are excluded from the study.

An informed parental consent is obtained at the initial post-natal visit. Each neonate is then randomly assigned to the placebo or intervention group per the block randomization generated using a computer-generated allocation sequence. Allocation is concealed from all involved investigators, bedside nurses, doctors, parents and outcome assessors except the International Board Certified Lactation Consultant (IBCLC) assigned to allocate the intervention. The IBCLC is not an investigator in the study.

Intervention group:

Colostrum that is fresh or refrigerated is collected by the IBCLC and prepared using 1cc syringes which are labeled with patient identification data, date and time of milk expression. These syringes are concealed using adhesive silk tapes and handed over to the bedside nurse. The tip of the syringe is placed towards the posterior end of the buccal cavity, colostrum/breastmilk is slowly squirted in aliquots of 0.1 ml of the milk into the area . This is to be done slowly drop by drop over a 30 s period. The milk should not pool in the buccal cavity. If it pools, give a few seconds to get absorbed and the rest may be manually rubbed using a swab along the gums and the inner surface of the buccal cavity for 10 seconds with two strokes in each area. Repeat the procedure on the opposite side. If the colostrum was refrigerated the syringe may be kept in the warm incubator for five minutes before administering.

OIT will be initiated as soon after birth as colostrum is available no earlier than six hours of age and continued every 4 hours as available. OIT may be provided in babies who are kept nil per oral and is to be continued even when enteral feeding has been ordered to get a minimum of 20 doses and can be continued until the baby reaches full oral feeding.

Control group: The control group will receive 0.2 ml of sterile water that will be prepared and applied in an identical manner and frequency to that among the intervention group. This will be started at six hours of age to avoid disclosure of intervention and control group. However, as soon as Mother's milk is available it will be initiated enterally.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: the intervention is carried out among preterm babies below 33 weeks of gestation or weight less than 1500gm
• Masking: Double (Care Provider, Investigator)

Masking Description

Block size and number of blocks: the sample size estimated for the study was 48 the size of the blocks is fixed in nature. Hence there are 6 blocks with a block size of 8 preterm babies each in every block.

Allocation ratio: one to one allocation ratio will be used for the study. Since the block size is 8 and one to one allocation was used, each block consist of 4 babies in each group (experimental:4, control =4) Sequence generation: 6 sets of random sequence will be generated with the help of research randomizer, an online random number generator. The sequence will be generated by an external member, who was not directly involved in the study.

Allocation concealment: Concealed allocation was achieved using sequentially Numbered, Opaque, Sealed Envelopes (SNOSESs). SNOSESs were prepared by an external member, who was not a part of study and kept in an opaque envelope.

Blinding: is done by covering the syringe with adhesive silk tape.

• Primary Purpose: Prevention
• Official Title: Effectiveness of Mother's Own Colostrum and Breast Milk as Oral Immunotherapy and on the Feeding Behaviors and Clinical Outcome Among Preterm Infants
• Actual Study Start Date: August 16, 2018
• Actual Primary Completion Date: December 28, 2018
• Actual Study Completion Date: December 28, 2018

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Sterile water; Sterile water: Started by six hours of age, In the control arm, 0.2 ml of sterile water is instilled into the posterior buccal cavity in aliquots of 0.1 ml over a 30 second period. The liquid is given time to get absorbed, any pooled liquid is swabbed in the infants' cheek and gum. This is performed every 4 hours until independent safe cup feeds, breastfeed or bottle feed is established consistently for 48 hours.	Other: Sterile water; Placebo Comparator: Sterile water: 0.2 ml of sterile water is instilled into the posterior buccal cavity in aliquots of 0.1 ml over a 30 second period. The liquid is given time to get absorbed, any pooled liquid is swabbed in the infants' cheek and gum. This is performed every 4 hours until independent safe cup feeds, breastfeed or bottle feed is established consistently for 48 hours.; Other Name: Placebo
Experimental: Breastmilk; Breastmilk. This is started at 6 hours of age at the earliest; breast milk: 0.2 ml of mothers' own colostrum/ breast milk is instilled into the posterior buccal cavity in aliquots of 0.1 ml over a 30 second period. The colostrum is given time to get absorbed, any pooled milk is swabbed in the infants' cheek and gum. This is performed every 4 hours until independent safe cup feeds, breastfeed or bottle feed is established consistently for 48 hours.	Biological: Breastmilk; Experimental: Breastmilk: 0.2 ml of mothers' own colostrum/ breast milk is instilled into the posterior buccal cavity in aliquots of 0.1 ml over a 30 second period. The colostrum is given time to get absorbed, any pooled milk is swabbed in the infants' cheek and gum. This is performed every 4 hours until independent safe cup feeds, breastfeed or bottle feed is established consistently for 48 hours. independently sucks at breast, bottle or cup feed; Other Name: experimental

Outcome Measures

Primary Outcome Measures :

1. Feeding Behaviors [ Time Frame: Birth to 45 weeks post menstrual age ]
   feeding behaviour is assessed using a questionaire on feeding behaviour. it consist of feed interruptions due to intolerance, time to reach full enteral feeding, time to independent oral feeds via direct breastfeed, cup or syringe feed or bottle feed consistently for 48 hours safely.

Secondary Outcome Measures :

1. Late onset sepsis [ Time Frame: Birth to 45 weeks post menstrual age ]
   late onset sepsis is measured using questionnaire on clinical outcome . it consist of culture proven sepsis and number of episodes.

Eligibility Criteria

• Ages Eligible for Study: up to 4 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Preterm babies below 33 weeks (32+6) weeks of gestation
• Birth weight <1500 g

Exclusion Criteria:

• Preterm babies with congenital anomalies
• Preterm babies with congenital infection like pneumonia.
• Babies born in other hospitals
• Babies of single mothers with unknown partners
• Confirmed immunodeficiency disorder,
• Inborn Error of Metabolism,
• Parental refusal to participate.
• Preterm babies who have overt bleeding

Contacts and Locations

Locations

Kuwait

Shiney Easo

Kuwait, Kuwait

Sponsors and Collaborators

Al Adan Hospital Kuwait

Investigators

• Principal Investigator: Shiney Easo, masters; AL Adan Hospital

More Information

• Responsible Party: Shiney Easo, Staff Nurse,, Al Adan Hospital Kuwait
• ClinicalTrials.gov Identifier: NCT03633500
• Other Study ID Numbers: 545/2017
• First Posted: August 16, 2018
• Last Update Posted: July 12, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shiney Easo, Al Adan Hospital Kuwait:

Colostrum; Oral immune therapy; Preterm; Oral feeding; Sepsis

Additional relevant MeSH terms:

Neonatal Sepsis; Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Infant, Newborn, Diseases