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NCT01954082: INS-3

Inositol to Reduce Retinopathy of Prematurity

Terminated Phase 3 Results posted Last updated 22 March 2019
What this trial tests

Phase 3 trial testing myo-Inositol 5% Injection in Retinopathy of Prematurity (ROP) in 638 participants. Terminated before completion.

Timeline
17 April 2014
Primary endpoint
31 December 2016
31 December 2016

Quick facts

Lead sponsorNICHD Neonatal Research Network
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposeprevention
Enrollment638
Start date17 April 2014
Primary completion31 December 2016
Estimated completion31 December 2016
Sites19 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

NICHD Neonatal Research Network

Who can join

Adults 12 Hours to 72 Hours, any sex, with Retinopathy of Prematurity (ROP). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Unfavorable Outcome, Defined as Severe Retinopathy of Prematurity (ROP) or Death Prior to Reaching Acute/Final ROP Status Primary · by 55 weeks PMA

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 r

GroupValue95% CI
Myo-Inositol 5% Injection91
5% Glucose(Dextrose)66
Number of Participants With Bronchopulmonary Dysplasia (BPD) Secondary · 36 weeks PMA

BPD is defined as supplemental oxygen required to maintain an oxygenation saturation of \>90% at 36 weeks postmenstrual age (PMA) (NICHD physiologic definition).

GroupValue95% CI
Myo-Inositol 5% Injection159
5% Glucose(Dextrose)165
Number of Participants With Bronchopulmonary Dysplasia (BPD) or Death From BPD Secondary · prior to 37 weeks PMA

BPD is defined as supplemental oxygen required to maintain an oxygenation saturation of \>90% at 36 weeks PMA (NICHD physiologic definition). Death from BPD prior to 37 weeks postmenstrual age (PMA) is defined when the cause of death is certified by the Center PI as BPD being the primary cause, or a significant co-contributing cause of death.

GroupValue95% CI
Myo-Inositol 5% Injection203
5% Glucose(Dextrose)195
Number of Participants With All Cause Death Before Retinopathy of Prematurity (ROP) Endpoint Secondary · by 55 weeks PMA age

Defined as death from any cause following randomization through primary study follow-up (up to 55 weeks postmenstrual age (PMA))

GroupValue95% CI
Myo-Inositol 5% Injection50
5% Glucose(Dextrose)33
Number of Participants With Any Retinopathy of Prematurity (ROP) Secondary · by 55 weeks PMA

ROP was identified by routine ophthalmologic examinations beginning at the latter of 31 weeks PMA or 4-6 weeks chronologic age. Any ROP is defined as ROP of any severity that is observed on at least 2 independent examinations in either eye through the time that Acute/Final ROP status is reached (up to 55 weeks postmenstrual age (PMA)).

GroupValue95% CI
Myo-Inositol 5% Injection171
5% Glucose(Dextrose)183
Number of Participants With Type 2 or More Severe Retinopathy of Prematurity (ROP) Secondary · by 55 weeks PMA

Defined as one or both eyes reaching Type 2 ROP (ETROP 2003) or the more severe Type 1 ROP (as defined previously) through the time that Acute/Final ROP status is reached (up to 55 weeks postmenstrual age (PMA)). Type 2 ROP is defined as (ETROP 2003): Stage 3 ROP without Plus Disease (i.e. Zone II) or Stage 1 or 2 ROP without Plus Disease (i.e. Zone I).

GroupValue95% CI
Myo-Inositol 5% Injection125
5% Glucose(Dextrose)142
Number of Participants With Severe Intraventricular Hemorrhage (IVH) Secondary · by 28 days PMA

Severe IVH is defined as IVH Grades 3 or 4 on either side of the brain. The evaluation for IVH occurs early (within 28 days from birth) via a cranial sonogram and is classified as described by Papile.

GroupValue95% CI
Myo-Inositol 5% Injection51
5% Glucose(Dextrose)50

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events will be recorded from treatment initiation until 7 days after the last dose of study drug, up to the earliest of 34 weeks post-menstrual age (PMA), 10 weeks chronologic age (CA), or discharge.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Myo-Inositol 5% Injection
Serious: 113/313 (36%)
Deaths: 50/317
5% Glucose(Dextrose)
Serious: 105/319 (33%)
Deaths: 33/321

Serious adverse events (51 terms)

ReactionSystemMyo-Inositol 5% Injection5% Glucose(Dextrose)
SYSTEMIC INFECTIONInfections and infestations
IVHNervous system disorders
POOR PERFUSION OR HYPOTENSIONCardiac disorders
SPONTANEOUS INTESTINAL PERFORATION, WITHOUT NECGastrointestinal disorders
NECGastrointestinal disorders
PULMONARY HEMORRHAGERespiratory, thoracic and mediastinal disorders
ANEMIABlood and lymphatic system disorders
PDACardiac disorders
PULMONARY AIR LEAKRespiratory, thoracic and mediastinal disorders
RESPIRATORY DETERIORATIONRespiratory, thoracic and mediastinal disorders
OLIGURIARenal and urinary disorders
CHOLESTASISGastrointestinal disorders
THROMBOCYTOPENIABlood and lymphatic system disorders
HYPERGLYCEMIAMetabolism and nutrition disorders
NEUTROPENIABlood and lymphatic system disorders
HYPERKALEMIARenal and urinary disorders
RENAL FAILURERenal and urinary disorders
ELEVATED LIVER ENZYMESGastrointestinal disorders
SEIZURESNervous system disorders
ELEVATED CREATININERenal and urinary disorders
ESPHOGEAL PERFORATIONGastrointestinal disorders
ACIDOSISMetabolism and nutrition disorders
PULMONARY HYPERTENSIONRespiratory, thoracic and mediastinal disorders
BRADYCARDIACardiac disorders
HYPERTENSIONCardiac disorders
Other adverse events (79 terms — click to expand)

ReactionSystemMyo-Inositol 5% Injection5% Glucose(Dextrose)
ANEMIABlood and lymphatic system disorders
RESPIRATORY DETERIORATIONRespiratory, thoracic and mediastinal disorders
THROMBOCYTOSISBlood and lymphatic system disorders
PDACardiac disorders
SYSTEMIC INFECTIONInfections and infestations
HYPERGLYCEMIAMetabolism and nutrition disorders
HYPERBILIRUBINEMIABlood and lymphatic system disorders
DELAYED GASTRIC EMPTYINGGastrointestinal disorders
HYPERKALEMIARenal and urinary disorders
OLIGURIARenal and urinary disorders
DIURESISRenal and urinary disorders
POOR PERFUSION OR HYPOTENSIONCardiac disorders
CHOLEOSTASISGastrointestinal disorders
IVHNervous system disorders
THROMBOCYTOPENIABlood and lymphatic system disorders
NEUTROPENIABlood and lymphatic system disorders
PULMONARY AIR LEAKRespiratory, thoracic and mediastinal disorders
HYPERTENSIONCardiac disorders
CONGESTIVE HEART FAILURECardiac disorders
ELEVATED LIVER ENZYMERSGastrointestinal disorders
SUPERFICIAL INFECTIONInfections and infestations
ELEVATED CREATININERenal and urinary disorders
NECGastrointestinal disorders
HEMATURIARenal and urinary disorders
PROTEINURIARenal and urinary disorders
TACHYCARDIACardiac disorders
HYPOGLYCEMIAMetabolism and nutrition disorders
LOCAL INFECTIONInfections and infestations
SEIZURESNervous system disorders
CHRONIC LUNG DISEASERespiratory, thoracic and mediastinal disorders
GLUCOSUIRARenal and urinary disorders
PULMONARY HEMORRHAGERespiratory, thoracic and mediastinal disorders
SKIN BREAKDOWNSkin and subcutaneous tissue disorders
HYPONATREMIAMetabolism and nutrition disorders
OSTEOPENIAMusculoskeletal and connective tissue disorders
RASHSkin and subcutaneous tissue disorders
ACIDOSISMetabolism and nutrition disorders
DIARRHEAGastrointestinal disorders
EMESISGastrointestinal disorders
ELECTROLYTE IMBALANCEMetabolism and nutrition disorders

Most-reported serious reactions: SYSTEMIC INFECTION, IVH, POOR PERFUSION OR HYPOTENSION, SPONTANEOUS INTESTINAL PERFORATION, WITHOUT NEC, NEC, PULMONARY HEMORRHAGE, ANEMIA, PDA.

Data from ClinicalTrials.gov NCT01954082 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Retinopathy of prematurity: a review of risk factors and their clinical significance.
    Kim SJ, Port AD, Swan R, Campbell JP, et al · · 2018 · cited 375× · PMID 29679617 · DOI 10.1016/j.survophthal.2018.04.002
  2. Advances in understanding and management of retinopathy of prematurity.
    Hartnett ME. · · 2017 · cited 100× · PMID 28012875 · DOI 10.1016/j.survophthal.2016.12.004
  3. Pharmacologic interventions for the prevention and treatment of retinopathy of prematurity.
    Beharry KD, Valencia GB, Lazzaro DR, Aranda JV. · · 2016 · cited 45× · PMID 26831641 · DOI 10.1053/j.semperi.2015.12.006
  4. Inositol in preterm infants at risk for or having respiratory distress syndrome.
    Howlett A, Ohlsson A, Plakkal N. · · 2019 · cited 26× · PMID 31283839 · DOI 10.1002/14651858.cd000366.pub4
  5. Role of cytokines and treatment algorithms in retinopathy of prematurity.
    Hartnett ME. · · 2017 · cited 12× · PMID 28141765 · DOI 10.1097/icu.0000000000000360
  6. Pediatric ocular nanomedicines: Challenges and opportunities.
    Sheybani ND, Yang H. · · 2017 · cited 11× · PMID 29147075 · DOI 10.1016/j.cclet.2017.07.022
  7. Early neurodevelopmental follow-up in the NICHD neonatal research network: Advancing neonatal care and outcomes, opportunities for the future.
    Kilbride HW, Vohr BR, McGowan EM, Peralta-Carcelen M, et al · · 2022 · cited 9× · PMID 35842320 · DOI 10.1016/j.semperi.2022.151642
  8. Relationships between retinopathy of prematurity without ophthalmologic intervention and neurodevelopment and vision at 2 years.
    Brumbaugh JE, Bell EF, Hirsch SC, Crenshaw EG, et al · · 2023 · cited 8× · PMID 34686832 · DOI 10.1038/s41390-021-01778-y

Verify or expand the search:

Other recruiting trials for Retinopathy of Prematurity (ROP)

Currently open trials in the same condition.

Other NICHD Neonatal Research Network trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing