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NCT02375971: RAINBOW

RAINBOW Study: RAnibizumab Compared With Laser Therapy for the Treatment of INfants BOrn Prematurely With Retinopathy of Prematurity

Completed Phase 3 Results posted Last updated 14 November 2018
What this trial tests

Phase 3 trial testing Ranibizumab in Retinopathy of Prematurity in 224 participants. Completed in 14 December 2017.

Timeline
30 December 2015
Primary endpoint
14 December 2017
14 December 2017

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment224
Start date30 December 2015
Primary completion14 December 2017
Estimated completion14 December 2017
Sites86 locations across Italy, Japan, Malaysia, Taiwan, Poland, Croatia, Denmark, Russia

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Eligibility, any sex, with Retinopathy of Prematurity. 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.

Percentage of Participants With Absence of Active ROP and Absence of Unfavorable Structural Outcomes in Both Eyes at Week 24 Primary · Week 24

To achieve this outcome, patients must fulfill all the following criteria, 1) survival, 2) no intervention with a second modality for ROP, 3) absence of active ROP and 4) absence of unfavorable structural outcome. Retinopathy of prematurity (ROP) is a pathologic process that occurs in the incompletely vascularized, developing retina of low birth-weight preterm neonates.

GroupValue95% CI
Ranibizumab 0.2 mg80.0
Ranibizumab 0.1 mg75.0
Laser Therapy66.2
Percentage of Participants Requiring Interventions With a Second Modality for ROP at Week 24 Secondary · Week 24

Intervention for ROP in either eye at or before the 24-week assessment visit with a treatment modality other than the modality of the first study treatment. Only descriptive analysis done.

GroupValue95% CI
Ranibizumab 0.2 mg14.9
Ranibizumab 0.1 mg16.9
Laser Therapy24.3
Number of Participants Experiencing an Event, From the First Study Treatment to the Last Study Visit Secondary · Day 1 (after initiation of study treatment) up to study exit (Day 169)

An event was defined as death, treatment switch, or the first occurrence of unfavorable structural outcomes in either eye. Only descriptive analysis done.

GroupValue95% CI
Ranibizumab 0.2 mg14
Ranibizumab 0.1 mg18
Laser Therapy23
Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24 Secondary · Week 24

Recurrence of ROP is defined as subjects receiving any post-baseline intervention in either eye at or before 24 weeks (ranibizumab re-treatment or switch to laser in the ranibizumab groups, switch to ranibizumab treatment in the laser group). Zone I consists of a circle, the radius of which extends from the center of the optic disc to twice the distance from the center of the optic disc to the center of the macula. Zone II extends centrifugally from the edge of zone I to the nasal ora serrata. Only descriptive analysis done.

All participants
GroupValue95% CI
Ranibizumab 0.2 mg31.1
Ranibizumab 0.1 mg31.2
Laser Therapy18.9
ZONE I
GroupValue95% CI
Ranibizumab 0.2 mg35.7
Ranibizumab 0.1 mg53.3
Laser Therapy28.6
ZONE II
GroupValue95% CI
Ranibizumab 0.2 mg28.3
Ranibizumab 0.1 mg17.4
Laser Therapy13.0
Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 Secondary · Week 24

Percent of Participants with Ocular Adverse Events regardless of Study Treatment and Procedure Relationship by Primary System Organ (SOCs) reported categorically (Mild, Moderate, Severe) 24 weeks after the first study treatment. Only descriptive analysis done.

Mild
GroupValue95% CI
Ranibizumab 0.2 mg23.3
Ranibizumab 0.1 mg32.9
Laser Therapy17.4
Moderate
GroupValue95% CI
Ranibizumab 0.2 mg4.1
Ranibizumab 0.1 mg6.6
Laser Therapy13.0
Severe
GroupValue95% CI
Ranibizumab 0.2 mg2.7
Ranibizumab 0.1 mg1.3
Laser Therapy2.9
Mean Change in Ranibizumab Concentration in Pharmacokinetic Serum Samples Over Time at Day 1, Day 15 and Day 29 Secondary · Day 1 (Baseline), Day 15 and Day 29

Blood samples for the determination of ranibizumab concentrations were collected in the Ranibizumab treatment arms only at the following time points: within 24 hours after the first administration of ranibizumab, at Day 15 and at Day 29. Only descriptive analysis done.

Day 1 (Baseline)
GroupValue95% CI
Ranibizumab 0.2 mg24700.0± 52400.00
Ranibizumab 0.1 mg12100.0± 25500.0
Day 15
GroupValue95% CI
Ranibizumab 0.2 mg5830.0± 4750.0
Ranibizumab 0.1 mg27700.0± 144000
Day 29
GroupValue95% CI
Ranibizumab 0.2 mg1810.0± 2990.0
Ranibizumab 0.1 mg732.0± 535.0
Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 Secondary · Day 1 (Baseline), Day 15 and Day 29

Blood samples for the determination of systemic VEGF levels were collected at the following time points: before the first investigational treatment, at Day 15 and at Day 29. Only descriptive analysis done.

Day 1
GroupValue95% CI
Ranibizumab 0.2 mg239.0± 226.0
Ranibizumab 0.1 mg230.0± 224.0
Laser Therapy232.0± 240.0
Day 1 / no treatment modality switch
GroupValue95% CI
Ranibizumab 0.2 mg239.0± 226.0
Ranibizumab 0.1 mg239.0± 233.0
Laser Therapy233.0± 245.0
Day 15
GroupValue95% CI
Ranibizumab 0.2 mg466.0± 1500.0
Ranibizumab 0.1 mg118.0± 129.0
Laser Therapy180.0± 214.0
Day 15 / no treatment modality switch
GroupValue95% CI
Ranibizumab 0.2 mg498.0± 1560.0
Ranibizumab 0.1 mg124.0± 134.0
Laser Therapy177.0± 224.0
Day 29
GroupValue95% CI
Ranibizumab 0.2 mg117.0± 84.0
Ranibizumab 0.1 mg176.0± 142.0
Laser Therapy161.0± 132.0
Day 29 / no treatment modality switch
GroupValue95% CI
Ranibizumab 0.2 mg117.0± 84.0
Ranibizumab 0.1 mg139.0± 75.3
Laser Therapy163.0± 138.0
Total Number of Ranibizumab Injections Received at Week 24 Secondary · Week 24

Patients randomized to receive Ranibizumab 0.1 mg or 0.2 mg received a single dose of intravitreal Ranibizumab to each eye on Day 1 (Baseline). Only descriptive analysis done.

GroupValue95% CI
Ranibizumab 0.2 mg73
Ranibizumab 0.1 mg76
Laser Therapy13
Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 Secondary · Week 24

Percent of Participants with Non-Ocular Adverse Events regardless of Study Treatment and Procedure Relationship by Primary System Organ (SOCs) reported categorically (Mild, Moderate, Severe) 24 weeks after the first study treatment. Only descriptive analysis done.

Mild
GroupValue95% CI
Ranibizumab 0.2 mg37.0
Ranibizumab 0.1 mg27.6
Laser Therapy31.9
Moderate
GroupValue95% CI
Ranibizumab 0.2 mg24.7
Ranibizumab 0.1 mg34.2
Laser Therapy27.5
Severe
GroupValue95% CI
Ranibizumab 0.2 mg23.3
Ranibizumab 0.1 mg19.7
Laser Therapy17.4
Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 Secondary · Baseline, Day 85, Day 169

Body Length, Head Circumference and Knee to Heel Length were assessed. Only descriptive analysis done.

Day 85 / Body Length
GroupValue95% CI
Ranibizumab 0.2 mg10.1± 2.59
Ranibizumab 0.1 mg11.0± 3.33
Laser Therapy11.1± 3.65
Day 169 / Body Length
GroupValue95% CI
Ranibizumab 0.2 mg18.7± 3.28
Ranibizumab 0.1 mg18.6± 3.66
Laser Therapy19.0± 4.50
Day 85 / Head Circumference
GroupValue95% CI
Ranibizumab 0.2 mg6.9± 1.96
Ranibizumab 0.1 mg6.5± 2.31
Laser Therapy7.2± 2.13
Day 169 / Head Circumference
GroupValue95% CI
Ranibizumab 0.2 mg10.4± 2.12
Ranibizumab 0.1 mg10.3± 2.56
Laser Therapy10.6± 2.61
Day 85 / Knee to Heel Length
GroupValue95% CI
Ranibizumab 0.2 mg2.9± 1.90
Ranibizumab 0.1 mg3.1± 1.65
Laser Therapy3.1± 2.02
Day 169 / Knee to Heel Length
GroupValue95% CI
Ranibizumab 0.2 mg5.4± 2.86
Ranibizumab 0.1 mg5.1± 2.19
Laser Therapy5.3± 2.15
Mean Change From Baseline in Vital Signs (Weight) at Day 85 and Day 169 Secondary · Baseline, Day 85, Day 169

Body weight was measured. Only descriptive analysis done.

Day 85 / Weight
GroupValue95% CI
Ranibizumab 0.2 mg2198.9± 615.68
Ranibizumab 0.1 mg2149.9± 754.27
Laser Therapy2182.7± 612.70
Day 169 / Weight
GroupValue95% CI
Ranibizumab 0.2 mg3794.3± 782.48
Ranibizumab 0.1 mg3716.7± 897.15
Laser Therapy3826.0± 882.17
Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 Secondary · Baseline, Day 85, Day 169

Blood Pressure measurements were not required by the protocol. Instead, the most recent Systolic and Diastolic Blood Pressure expressed in millimeters of mercury (mmHg) measured as part of the routine clinical care were used. Only descriptive analysis done.

Day 85 / Sitting Diastolic Blood Pressure
GroupValue95% CI
Ranibizumab 0.2 mg8.1± 14.66
Ranibizumab 0.1 mg7.0± 14.25
Laser Therapy9.8± 16.95
Day 85 / Sitting Systolic Blood Pressure
GroupValue95% CI
Ranibizumab 0.2 mg6.3± 15.85
Ranibizumab 0.1 mg9.4± 15.73
Laser Therapy15.5± 16.85
Day 169 / Sitting Diastolic Blood Pressure
GroupValue95% CI
Ranibizumab 0.2 mg11.5± 15.60
Ranibizumab 0.1 mg11.8± 14.42
Laser Therapy14.7± 17.05
Day 169 / Sitting Systolic Blood Pressure
GroupValue95% CI
Ranibizumab 0.2 mg10.2± 16.15
Ranibizumab 0.1 mg11.2± 13.45
Laser Therapy17.7± 19.35

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit).. Reporting threshold: 4%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ranibizumab 0.2 mg
Serious: 26/73 (36%)
Deaths: 4/73
Ranibizumab 0.1 mg
Serious: 24/76 (32%)
Deaths: 4/76
Laser
Serious: 24/69 (35%)
Deaths: 4/69

Serious adverse events (96 terms)

ReactionSystemRanibizumab 0.2 mgRanibizumab 0.1 mgLaser
BronchiolitisInfections and infestations
PneumoniaInfections and infestations
Retinopathy of prematurityEye disorders
Necrotising colitisGastrointestinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Cardio-respiratory arrestCardiac disorders
DiarrhoeaGastrointestinal disorders
Incarcerated inguinal herniaGastrointestinal disorders
Inguinal herniaGastrointestinal disorders
VomitingGastrointestinal disorders
NasopharyngitisInfections and infestations
SepsisInfections and infestations
Brain oedemaNervous system disorders
Perinatal brain damagePregnancy, puerperium and perinatal conditions
ApnoeaRespiratory, thoracic and mediastinal disorders
Bronchopulmonary dysplasiaRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
ArrhythmiaCardiac disorders
Cardiac arrestCardiac disorders
Cardiac failureCardiac disorders
Cardiogenic shockCardiac disorders
Cardiopulmonary failureCardiac disorders
HydroceleCongenital, familial and genetic disorders
Ileal atresiaCongenital, familial and genetic disorders
CataractEye disorders
Other adverse events (24 terms — click to expand)

ReactionSystemRanibizumab 0.2 mgRanibizumab 0.1 mgLaser
Retinal haemorrhageEye disorders
PyrexiaGeneral disorders
AnaemiaBlood and lymphatic system disorders
Dermatitis diaperSkin and subcutaneous tissue disorders
NasopharyngitisInfections and infestations
Conjunctival haemorrhageEye disorders
ConjunctivitisInfections and infestations
PneumoniaInfections and infestations
Upper respiratory tract infectionInfections and infestations
BradycardiaCardiac disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Anaemia neonatalBlood and lymphatic system disorders
Vitreous haemorrhageEye disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
OsteopeniaMusculoskeletal and connective tissue disorders
ApnoeaRespiratory, thoracic and mediastinal disorders
Bronchopulmonary dysplasiaRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Inguinal herniaGastrointestinal disorders
RhinitisInfections and infestations
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
BronchospasmRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Bronchiolitis, Pneumonia, Retinopathy of prematurity, Necrotising colitis, Respiratory failure, Cardio-respiratory arrest, Diarrhoea, Incarcerated inguinal hernia.

Data from ClinicalTrials.gov NCT02375971 adverse events section.

Sponsor's own description

The purpose of this study was to determine if intravitreal ranibizumab is superior to laser ablation therapy in the treatment of retinopathy of prematurity (ROP).

Publications & conference data

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

  1. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial.
    Stahl A, Lepore D, Fielder A, Fleck B, et al · · 2019 · cited 291× · PMID 31522845 · DOI 10.1016/s0140-6736(19)31344-3
  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. A review of treatment for retinopathy of prematurity.
    Hansen ED, Hartnett ME. · · 2019 · cited 28× · PMID 31762784 · DOI 10.1080/17469899.2019.1596026
  4. Retinopathy of prematurity in the United Kingdom: retreatment rates, visual and structural 1-year outcomes.
    Adams GG, Bunce C, Xing W, Butler L, et al · · 2018 · cited 15× · PMID 30013158 · DOI 10.1038/s41433-018-0151-y
  5. Role of cytokines and treatment algorithms in retinopathy of prematurity.
    Hartnett ME. · · 2017 · cited 12× · PMID 28141765 · DOI 10.1097/icu.0000000000000360
  6. Evidence to date: ranibizumab and its potential in the treatment of retinopathy of prematurity.
    Patel SN, Klufas MA. · · 2019 · cited 11× · PMID 31693715 · DOI 10.2147/eb.s189684
  7. Different Types of Hyperfluorescence Observed in Post Anti-VEGF Fluorescein Angiographic Patterns in Retinopathy of Prematurity Patients.
    Jin E, Yin H, Liu K, Liang Z, et al · · 2021 · cited 2× · PMID 35141247 · DOI 10.3389/fmed.2021.800821

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02375971.

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