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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02375971
Recruitment Status : Completed
First Posted : March 3, 2015
Results First Posted : July 31, 2018
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE February 18, 2015
First Posted Date  ICMJE March 3, 2015
Results First Submitted Date  ICMJE June 5, 2018
Results First Posted Date  ICMJE July 31, 2018
Last Update Posted Date November 14, 2018
Actual Study Start Date  ICMJE December 30, 2015
Actual Primary Completion Date December 14, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 3, 2018)
Percentage of Participants With Absence of Active ROP and Absence of Unfavorable Structural Outcomes in Both Eyes at Week 24 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 24, 2015)
Absence of active Retinopathy of Prematurity (ROP) and unfavorable structural outcome [ Time Frame: 24 weeks after starting investigational treatment ]
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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2018)
  • Percentage of Participants Requiring Interventions With a Second Modality for ROP at Week 24 [ Time Frame: 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.
  • Number of Participants Experiencing an Event, From the First Study Treatment to the Last Study Visit [ Time Frame: 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.
  • Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24 [ Time Frame: 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.
  • Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 [ Time Frame: 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.
  • Mean Change in Ranibizumab Concentration in Pharmacokinetic Serum Samples Over Time at Day 1, Day 15 and Day 29 [ Time Frame: 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.
  • Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29 [ Time Frame: 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.
  • Total Number of Ranibizumab Injections Received at Week 24 [ Time Frame: 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.
  • Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24 [ Time Frame: 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.
  • Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169 [ Time Frame: Baseline, Day 85, Day 169 ]
    Body Length, Head Circumference and Knee to Heel Length were assessed. Only descriptive analysis done.
  • Mean Change From Baseline in Vital Signs (Weight) at Day 85 and Day 169 [ Time Frame: Baseline, Day 85, Day 169 ]
    Body weight was measured. Only descriptive analysis done.
  • Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 24, 2015)
  • Requirement for intervention with a second modality for ROP [ Time Frame: 24 weeks after starting investigational treatment ]
  • Time to intervention with a second modality for ROP or development of unfavorable structural outcome or death [ Time Frame: 24 weeks after starting investigational treatment ]
  • Recurrence of ROP [ Time Frame: 24 weeks after starting investigational treatment ]
  • Number of patients having any ocular Adverse Event [ Time Frame: 24 weeks after starting investigational treatment ]
  • Systemic ranibizumab levels [ Time Frame: Within 24 hours, 14 days and 28 days after ranibizumab treatment ]
  • Systemic Vascular Endothelial Growth Factor (VEGF) levels [ Time Frame: Before investigational treatment, 14 days and 28 days after investigational treatment ]
  • Number of ranibizumab administrations [ Time Frame: 24 weeks after starting investigational treatment ]
  • Number of patients having any systemic Adverse Event [ Time Frame: 24 weeks after starting investigational treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE RAINBOW Study: RAnibizumab Compared With Laser Therapy for the Treatment of INfants BOrn Prematurely With Retinopathy of Prematurity
Official Title  ICMJE RAINBOW Study: a Randomized, Controlled Study Evaluating the Efficacy and Safety of RAnibizumab Compared With Laser Therapy for the Treatment of INfants BOrn Prematurely With Retinopathy of Prematurity
Brief Summary 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).
Detailed Description The study consisted of a screening period (screening and randomization could occur up to 3 days before the administration of the first investigational treatment), followed by a treatment and follow-up period (Day 1 to Day 169).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Retinopathy of Prematurity
Intervention  ICMJE
  • Drug: Ranibizumab
    Administered as an intravitreal injection
  • Procedure: Laser therapy
    Transpupillary diode or frequency-doubled yttrium aluminum garnet (YAG) laser ablative therapy, following anesthesia or sedation
Study Arms  ICMJE
  • Experimental: Ranibizumab 0.2 mg
    1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
    Intervention: Drug: Ranibizumab
  • Experimental: Ranibizumab 0.1 mg
    1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
    Intervention: Drug: Ranibizumab
  • Active Comparator: Laser therapy
    Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
    Intervention: Procedure: Laser therapy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 29, 2017)
224
Original Estimated Enrollment  ICMJE
 (submitted: February 24, 2015)
300
Actual Study Completion Date  ICMJE December 14, 2017
Actual Primary Completion Date December 14, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • preterm infants with a birth weight of less than 1500 g
  • bilateral ROP with one of the following retinal findings in each eye: Zone I, stage 1+, 2+, 3 or 3+ disease, or Zone II, stage 3+ disease, or Aggressive posterior retinopathy of prematurity (AP-ROP)

Exclusion Criteria:

  • ROP disease characteristic in either eye other than that listed above at the time of the first investigational treatment
  • A history of hypersensitivity (either the patient or the mother) to any of the investigational treatments or to drugs of similar chemical classes
  • Had received any previous surgical or nonsurgical treatment for ROP (e.g., ablative laser therapy or cryotherapy, vitrectomy)
  • Had been previously exposed to any intravitreal or systemic anti-VEGF agent (either the patient or the mother during this child's pregnancy)
  • Had used (either the patient or the mother) other investigational drugs as part of another clinical study (other than vitamins and minerals) within 30 days or within 5 half-lives of the other investigational drug, whichever was longer
  • Had ocular structural abnormalities that were assessed by the Investigator to have had a clinically significant impact on study assessments
  • Had active ocular infection within 5 days before or on the day of first investigational treatment
  • Had a history of hydrocephalus requiring treatment
  • Had a history of any other neurological conditions that are assessed by the Investigator to have a significant risk of severe impact on visual function
  • Had any other medical conditions or clinically significant comorbidities or personal circumstances that were assessed by the Investigator to have a clinically relevant impact on study participation, any of the study procedures, or on efficacy assessments (e.g., poor life expectancy, pupil not able to be adequately dilated, unable to comply with the visit schedule)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Belgium,   Croatia,   Czechia,   Denmark,   Egypt,   Estonia,   France,   Germany,   Greece,   Hungary,   India,   Italy,   Japan,   Lithuania,   Malaysia,   Mexico,   Poland,   Romania,   Russian Federation,   Saudi Arabia,   Slovakia,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries Canada,   Chile,   Colombia,   Czech Republic,   Finland,   Sweden,   United Arab Emirates
 
Administrative Information
NCT Number  ICMJE NCT02375971
Other Study ID Numbers  ICMJE CRFB002H2301
2014-003041-10 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Current Responsible Party Novartis ( Novartis Pharmaceuticals )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Novartis Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP