Inositol to Reduce Retinopathy of Prematurity

NCT01954082 | Terminated Phase 3 Results DMC FDA Drug

• 20 other identifiers: NICHD-NRN-0053U10HD021364U10HD040689U10HD021385U10HD027851U10HD027853U10HD027856U10HD027904U10HD027880U10HD034216U10HD021373U10HD040492U10HD053109U10HD053089U10HD068244U10HD068263U10HD068270U10HD068278U10HD068284U10HD036790
• Study Type: interventional
• Target: 638
• Locations: 1 country
• Sites: 19

Brief Summary

This is a Phase 3, randomized, double-masked, placebo-controlled study designed to determine the effectiveness of myo-Inositol 5% Injection to increase the incidence of survival without severe Retinopathy of Prematurity (ROP) through acute/final ROP determination up to 55 weeks postmenstrual age (PMA) in premature infants \<28 0/7 weeks' gestation.

Conditions

Retinopathy of Prematurity (ROP)

Keywords

Retinopathy; Prematurity; Infant, Newborn, Diseases

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Unfavorable Outcome, Defined as Severe Retinopathy of Prematurity (ROP) or Death Prior to Reaching Acute/Final ROP Status

  Death is defined as from any cause before Acute/Final ROP status is determined. ROP was identified by routine ophthalmologic examinations beginning at the latter of 31 weeks PMA or 4-6 weeks chronologic age. The favorable ROP endpoint requires that no ROP, or only mild ROP has occurred in both eyes and the eyes have matured beyond the risk of developing Type 1 ROP (severity meeting criteria for surgical intervention). The unfavorable ROP endpoint requires that one or both eyes reach Type 1 ROP. When ROP did not resolve by the time of discharge, participants were followed as outpatients until reaching an ROP endpoint, up to 55 weeks PMA. Since incomplete follow up is more likely among participants with mild or no ROP than for those with aggressive ROP, an independent adjudication process assigned an ROP endpoint of 'most likely never had Type 1 ROP', or 'most likely developed Type 1 ROP' based on clinical and ROP data review to reduce possible missing data bias.

  by 55 weeks PMA

Secondary Outcomes (6)

• Number of Participants With Bronchopulmonary Dysplasia (BPD)

  36 weeks PMA

• Number of Participants With Bronchopulmonary Dysplasia (BPD) or Death From BPD

  prior to 37 weeks PMA

• Number of Participants With All Cause Death Before Retinopathy of Prematurity (ROP) Endpoint

  by 55 weeks PMA age

• Number of Participants With Any Retinopathy of Prematurity (ROP)

  by 55 weeks PMA

• Number of Participants With Type 2 or More Severe Retinopathy of Prematurity (ROP)

  by 55 weeks PMA

Other Outcomes (14)

• The Occurrence of Adverse Events and Serious Adverse Events

  7 days post study drug discontinuation

• Necrotizing Enterocolitis (NEC)

  NRN infant status, i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

• Isolated Gastrointestinal Perforation

  NRN infant status, i.e., the first occurring of: discharge home, death, transfer, or 120 days following birth

Study Arms (2)

myo-Inositol 5% Injection

EXPERIMENTAL

Within 12-72 hours of birth, infants will receive 80 mg myo-inositol 5% Injection per kilogram per day, administered in divided doses every 12 hours (40 mg/kg/dose). Study drug will be administered daily and continued until the earliest of 34 completed weeks PMA, 10 weeks (70 days) chronologic age, or the time of discharge. myo-Inositol 5% Injection will be administered IV until enteral feedings are established, at which time the same dose and formulation will be administered enterally every 12 hours.

Drug: myo-Inositol 5% Injection

5% glucose(dextrose)

PLACEBO COMPARATOR

Within 12-72 hours of birth, infants will receive 80 mg 5% glucose(dextrose) USP for intravenous infusion per kilogram per day, administered in divided doses every 12 hours (40 mg/kg/dose). Study drug will be administered daily and continued until the earliest of 34 completed weeks PMA, 10 weeks (70 days) chronologic age, or the time of discharge. myo-Inositol 5% Injection will be administered IV until enteral feedings are established, at which time the same dose and formulation will be administered enterally every 12 hours.

Drug: Placebo

Interventions

myo-Inositol 5% Injection DRUG

Abbott Nutrition Division, Abbott Laboratories is supplying myo-Inositol 5% Injection to the clinical centers for the duration of the trial. Inositol: myo-Inositol 5% Injection is an isotonic, preservative-free, sterile 5% solution of myo-inositol in water containing 0.5 gm sodium chloride per liter (8.55mM), pH 6.5-7.5. It is administered via IV infusion using syringe pump over 15-30 minutes twice per day at 12-hour intervals at a dose of 80 mg inositol/kg/day (40 mg inositol/kg/dose), which is equivalent to 1.6 mL/kg/day (0.80 mL/kg/dose).

Also known as: Inositol

myo-Inositol 5% Injection

Placebo DRUG

% glucose(dextrose)

5% glucose(dextrose)

Eligibility Criteria

• Age: 12 Hours - 72 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Inborn or out born infants of either gender or any race with best obstetrical estimate of gestation \<28 weeks (27 6/7 weeks and younger). Gestational age will be determined by best obstetrical estimate using the hierarchy of best obstetrical estimate using early ultrasound dating, maternal menstrual dating confirmed by examination, or neonatal gestational age assessment by physical examination.
• Alive at 12 hours.
• Age in hours up to 72 hours, although we will seek enrollment as early as feasible after consent and 12 hours.
• Informed consent signed and dated by parent and/or guardian, which includes likelihood of completing follow-up ophthalmic examinations as an outpatient, and long-term follow-up.

You may not qualify if:

• Major congenital malformations
• Congenital malformations of the eye identified prior to randomization.
• Overt evidence of intrauterine congenital infections ("TORCH") or life threatening impairment of renal, hepatic, or cardiac function (considered moribund).

Sponsors & Collaborators

• NICHD Neonatal Research Network: lead
• National Eye Institute (NEI): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (19)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of California - Los Angeles

Los Angeles, California, 90025, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

RTI International

Durham, North Carolina, 27705, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45267, United States

Location

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Research Institute at Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Univeristy of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Brown University, Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Brumbaugh JE, Bell EF, Hirsch SC, Crenshaw EG, DeMauro SB, Adams-Chapman IS, Lowe JR, Natarajan G, Wyckoff MH, Vohr BR, Colaizy TT, Harmon HM, Watterberg KL, Hintz SR; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Relationships between retinopathy of prematurity without ophthalmologic intervention and neurodevelopment and vision at 2 years. Pediatr Res. 2023 Nov;94(5):1720-1730. doi: 10.1038/s41390-021-01778-y. Epub 2021 Oct 22.

  PMID: 34686832 DERIVED

Related Links

• NICHD NRN Website
• NICHD Pregnancy \& Perinatology Branch

MeSH Terms

Conditions

Retinopathy of Prematurity; Retinal Diseases; Premature Birth; Infant, Newborn, Diseases

Interventions

Inositol; Injections

Condition Hierarchy (Ancestors)

Eye Diseases; Infant, Premature, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Drug Administration Routes; Drug Therapy; Therapeutics

Limitations and Caveats

Due to a manufacturing issue, enrollment and treatment were temporarily suspended pending review of primary outcome data for the enrolled infants. The statistically significant increase in mortality resulted in early study termination.

Results Point of Contact

• Title: Dale Phelps
• Organization: University of Rochester

dale_phelps@urmc.rochester.edu

(585) 275-2972

Study Officials

• Michele C Walsh, MD

  Case Western Reserve University, Rainbow Babies and Children's Hospital

  PRINCIPAL INVESTIGATOR

• Abhik Das, PhD

  RTI International

  PRINCIPAL INVESTIGATOR

• Seetha Shankaran, MD

  Wayne State University

  PRINCIPAL INVESTIGATOR

• Barbara J Stoll, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Kurt Schibler, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Greg Sokol, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

• Abbot R Laptook, MD

  Brown University, Women & Infants Hospital of Rhode Island

  PRINCIPAL INVESTIGATOR

• Krisa P Van Meurs, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Waldemar A Carlo, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Kathleen A Kennedy, MD, MPH

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

• Ronald N Goldberg, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Edward F Bell, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

• Dale L Phelps, MD

  University of Rochester

  STUDY DIRECTOR

• Carl T D'Angio, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

• William Truog, MD

  Children's Mercy Hospital Kansas City

  PRINCIPAL INVESTIGATOR

• Pablo Sanchez, MD

  Research Institute at Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

• Uday Devaskar, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Myra Wyckoff, MD

  University of Texas at Southwestern

  PRINCIPAL INVESTIGATOR

• Kristi L Watterberg, MD

  University of New Mexico

  PRINCIPAL INVESTIGATOR

• Barbara Schmidt, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2013
• First Posted: October 1, 2013
• Study Start: April 17, 2014
• Primary Completion: December 31, 2016
• Study Completion: December 31, 2016
• Last Updated: March 22, 2019
• Results First Posted: September 26, 2018

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: One year after primary publication
• Access Criteria: NICHD Data and Specimen Repository (DASH)

Locations

US (19)