Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Retinopathy of Prematurity
Interventions Drug: Ranibizumab
Procedure: Laser therapy
Enrollment 224
Recruitment Details This study was conducted in 87 sites: Austria(2), Belgium(2), Croatia(2), Czech Republic(3), Denmark(1), Egypt(1), Estonia(1), France(2), Germany(2), Greece(3), Hungary(2), India(6), Italy(4), Japan(17), Lithuania(1), Malaysia(2), Mexico(1), Poland(2), Romania(3), Russia(5), Saudi Arabia(1), Slovakia(1), Taiwan(2), Turkey(6), UK(3) and USA(12).
Pre-assignment Details One patient was discontinued prior to receiving any study treatment and was later re-randomized; this patient is counted twice in the Randomized Set (FAS) (225). The number of unique participants randomized in the study is 224.
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser Therapy
Hide Arm/Group Description 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Period Title: Treatment (Day 1 - Baseline)
Started [1] 74 77 74
Safety Set [2] 73 76 69
VEGF Set [3] 19 26 51
PK Set [4] 49 46 0
Completed [5] 73 76 69
Not Completed 1 1 5
Reason Not Completed
Subj/Guardian Decision             0             0             2
Physician Decision             1             1             1
Lost to Follow-up             0             0             1
Adverse Event             0             0             1
[1]
All randomized patients to whom treatment had been assigned (FAS)
[2]
At least 1 application of investigational treatment and a 1 post baseline safety assessment
[3]
All patients who provided valid Vascular endothelial growth factor (VEGF) plasma samples
[4]
All patients who provided Pharmacokinetics (PK) serum samples
[5]
All patients who completed the treatment phase
Period Title: Follow-Up Phase (up to Day 169)
Started [1] 73 76 69
Completed [2] 66 71 64
Not Completed 7 5 5
Reason Not Completed
Adverse Event             1             0             0
Subject/Guardian Decision             1             0             1
Death             4             4             4
Withdrawal of Consent             1             1             0
[1]
All patients who started the follow-up phase
[2]
All patients who completed the follow-up phase
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser Therapy Total
Hide Arm/Group Description 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed Total of all reporting groups
Overall Number of Baseline Participants 74 77 74 225
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 74 participants 77 participants 74 participants 225 participants
25.8  (2.25) 26.5  (2.57) 26.2  (2.59) 26.1  (2.48)
[1]
Measure Description: Gestational age at birth (weeks)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 74 participants 77 participants 74 participants 225 participants
Female
41
  55.4%
40
  51.9%
37
  50.0%
118
  52.4%
Male
33
  44.6%
37
  48.1%
37
  50.0%
107
  47.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 74 participants 77 participants 74 participants 225 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
27
  36.5%
22
  28.6%
23
  31.1%
72
  32.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
4
   5.2%
3
   4.1%
7
   3.1%
White
43
  58.1%
45
  58.4%
45
  60.8%
133
  59.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
4
   5.4%
6
   7.8%
3
   4.1%
13
   5.8%
1.Primary Outcome
Title Percentage of Participants With Absence of Active ROP and Absence of Unfavorable Structural Outcomes in Both Eyes at Week 24
Hide Description 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.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser Therapy
Hide Arm/Group Description:
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Overall Number of Participants Analyzed 74 77 74
Measure Type: Number
Unit of Measure: Percentage of Participants
80.0 75.0 66.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab 0.2 mg, Ranibizumab 0.1 mg, Laser Therapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The primary efficacy variable was treatment success, defined as the absence of active ROP and absence of unfavorable structural outcomes in both eyes 24 weeks after starting study treatment.
Statistical Test of Hypothesis P-Value 0.0254
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.19
Confidence Interval (2-Sided) 95%
0.9932 to 4.8235
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants Requiring Interventions With a Second Modality for ROP at Week 24
Hide Description 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.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser Therapy
Hide Arm/Group Description:
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Overall Number of Participants Analyzed 74 77 74
Measure Type: Number
Unit of Measure: Percentage of participants
14.9 16.9 24.3
3.Secondary Outcome
Title Number of Participants Experiencing an Event, From the First Study Treatment to the Last Study Visit
Hide Description An event was defined as death, treatment switch, or the first occurrence of unfavorable structural outcomes in either eye. Only descriptive analysis done.
Time Frame Day 1 (after initiation of study treatment) up to study exit (Day 169)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser Therapy
Hide Arm/Group Description:
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Overall Number of Participants Analyzed 74 77 74
Measure Type: Number
Unit of Measure: Participants
14 18 23
4.Secondary Outcome
Title Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before Week 24
Hide Description 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.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), which consisted of all participants with an observed value, was considered.
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser Therapy
Hide Arm/Group Description:
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Overall Number of Participants Analyzed 74 77 74
Measure Type: Number
Unit of Measure: Percentage of participants
All participants 31.1 31.2 18.9
ZONE I 35.7 53.3 28.6
ZONE II 28.3 17.4 13.0
5.Secondary Outcome
Title Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at Week 24
Hide Description 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.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set was considered.
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser Therapy
Hide Arm/Group Description:
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Overall Number of Participants Analyzed 73 76 69
Measure Type: Number
Unit of Measure: Percent of participants
Mild 23.3 32.9 17.4
Moderate 4.1 6.6 13.0
Severe 2.7 1.3 2.9
6.Secondary Outcome
Title Mean Change in Ranibizumab Concentration in Pharmacokinetic Serum Samples Over Time at Day 1, Day 15 and Day 29
Hide Description 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.
Time Frame Day 1 (Baseline), Day 15 and Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
The PK Set, which consisted of all participants with at least one valid PK concentration value, was considered.
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg
Hide Arm/Group Description:
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
Overall Number of Participants Analyzed 49 46
Mean (Standard Deviation)
Unit of Measure: picogram/milliliter (pg/mL)
Day 1 (Baseline) Number Analyzed 43 participants 43 participants
24700.0  (52400.00) 12100.0  (25500.0)
Day 15 Number Analyzed 45 participants 36 participants
5830.0  (4750.0) 27700.0  (144000)
Day 29 Number Analyzed 31 participants 24 participants
1810.0  (2990.0) 732.0  (535.0)
7.Secondary Outcome
Title Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, Day 15 and Day 29
Hide Description 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.
Time Frame Day 1 (Baseline), Day 15 and Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
The VEGF Set, which consisted of all participants with at least one valid VEGF concentration value, was considered.
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser Therapy
Hide Arm/Group Description:
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Overall Number of Participants Analyzed 19 26 51
Mean (Standard Deviation)
Unit of Measure: picogram/milliliter (pg/mL)
Day 1 Number Analyzed 17 participants 21 participants 46 participants
239.0  (226.0) 230.0  (224.0) 232.0  (240.0)
Day 1 / no treatment modality switch Number Analyzed 17 participants 18 participants 41 participants
239.0  (226.0) 239.0  (233.0) 233.0  (245.0)
Day 15 Number Analyzed 15 participants 26 participants 44 participants
466.0  (1500.0) 118.0  (129.0) 180.0  (214.0)
Day 15 / no treatment modality switch Number Analyzed 14 participants 23 participants 38 participants
498.0  (1560.0) 124.0  (134.0) 177.0  (224.0)
Day 29 Number Analyzed 13 participants 18 participants 30 participants
117.0  (84.0) 176.0  (142.0) 161.0  (132.0)
Day 29 / no treatment modality switch Number Analyzed 13 participants 15 participants 27 participants
117.0  (84.0) 139.0  (75.3) 163.0  (138.0)
8.Secondary Outcome
Title Total Number of Ranibizumab Injections Received at Week 24
Hide Description 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.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set was considered.
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser Therapy
Hide Arm/Group Description:
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Overall Number of Participants Analyzed 73 76 69
Measure Type: Number
Unit of Measure: Injections
73 76 13
9.Secondary Outcome
Title Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at Week 24
Hide Description 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.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set was considered.
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser Therapy
Hide Arm/Group Description:
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Overall Number of Participants Analyzed 73 76 69
Measure Type: Number
Unit of Measure: Percent of participants
Mild 37.0 27.6 31.9
Moderate 24.7 34.2 27.5
Severe 23.3 19.7 17.4
10.Secondary Outcome
Title Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169
Hide Description Body Length, Head Circumference and Knee to Heel Length were assessed. Only descriptive analysis done.
Time Frame Baseline, Day 85, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set was considered. Only patients with evaluable data at each time point were analyzed for that time point.
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser Therapy
Hide Arm/Group Description:
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Overall Number of Participants Analyzed 73 76 69
Mean (Standard Deviation)
Unit of Measure: centimeter (cm)
Day 85 / Body Length Number Analyzed 61 participants 63 participants 60 participants
10.1  (2.59) 11.0  (3.33) 11.1  (3.65)
Day 169 / Body Length Number Analyzed 62 participants 62 participants 57 participants
18.7  (3.28) 18.6  (3.66) 19.0  (4.50)
Day 85 / Head Circumference Number Analyzed 62 participants 62 participants 59 participants
6.9  (1.96) 6.5  (2.31) 7.2  (2.13)
Day 169 / Head Circumference Number Analyzed 62 participants 62 participants 57 participants
10.4  (2.12) 10.3  (2.56) 10.6  (2.61)
Day 85 / Knee to Heel Length Number Analyzed 55 participants 51 participants 52 participants
2.9  (1.90) 3.1  (1.65) 3.1  (2.02)
Day 169 / Knee to Heel Length Number Analyzed 53 participants 52 participants 52 participants
5.4  (2.86) 5.1  (2.19) 5.3  (2.15)
11.Secondary Outcome
Title Mean Change From Baseline in Vital Signs (Weight) at Day 85 and Day 169
Hide Description Body weight was measured. Only descriptive analysis done.
Time Frame Baseline, Day 85, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set was considered. Only patients with evaluable data at each time point were analyzed for that time point.
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser Therapy
Hide Arm/Group Description:
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Overall Number of Participants Analyzed 73 76 69
Mean (Standard Deviation)
Unit of Measure: gram (g)
Day 85 / Weight Number Analyzed 63 participants 66 participants 60 participants
2198.9  (615.68) 2149.9  (754.27) 2182.7  (612.70)
Day 169 / Weight Number Analyzed 62 participants 62 participants 60 participants
3794.3  (782.48) 3716.7  (897.15) 3826.0  (882.17)
12.Secondary Outcome
Title Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and Day 169
Hide Description 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.
Time Frame Baseline, Day 85, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set was considered. Only patients with evaluable data at each time point were analyzed for that time point.
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser Therapy
Hide Arm/Group Description:
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Overall Number of Participants Analyzed 73 76 69
Mean (Standard Deviation)
Unit of Measure: millimeters of mercury (mmHg)
Day 85 / Sitting Diastolic Blood Pressure Number Analyzed 47 participants 46 participants 41 participants
8.1  (14.66) 7.0  (14.25) 9.8  (16.95)
Day 85 / Sitting Systolic Blood Pressure Number Analyzed 47 participants 46 participants 41 participants
6.3  (15.85) 9.4  (15.73) 15.5  (16.85)
Day 169 / Sitting Diastolic Blood Pressure Number Analyzed 45 participants 46 participants 40 participants
11.5  (15.60) 11.8  (14.42) 14.7  (17.05)
Day 169 / Sitting Systolic Blood Pressure Number Analyzed 45 participants 46 participants 40 participants
10.2  (16.15) 11.2  (13.45) 17.7  (19.35)
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).
Adverse Event Reporting Description Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
 
Arm/Group Title Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser
Hide Arm/Group Description 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required 1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required Laser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
All-Cause Mortality
Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/73 (5.48%)   4/76 (5.26%)   4/69 (5.80%) 
Show Serious Adverse Events Hide Serious Adverse Events
Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   26/73 (35.62%)   24/76 (31.58%)   24/69 (34.78%) 
Blood and lymphatic system disorders       
Anaemia  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Cardiac disorders       
Arrhythmia  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Cardiac arrest  1  0/73 (0.00%)  1/76 (1.32%)  1/69 (1.45%) 
Cardiac failure  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Cardio-respiratory arrest  1  0/73 (0.00%)  2/76 (2.63%)  0/69 (0.00%) 
Cardiogenic shock  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Cardiopulmonary failure  1  1/73 (1.37%)  1/76 (1.32%)  0/69 (0.00%) 
Congenital, familial and genetic disorders       
Hydrocele  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Ileal atresia  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Eye disorders       
Cataract  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Exophthalmos  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Eye disorder  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Retinopathy of prematurity  1  2/73 (2.74%)  1/76 (1.32%)  3/69 (4.35%) 
Gastrointestinal disorders       
Abdominal discomfort  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Diarrhoea  1  0/73 (0.00%)  2/76 (2.63%)  0/69 (0.00%) 
Gastrointestinal haemorrhage  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Gastrooesophageal reflux disease  1  0/73 (0.00%)  1/76 (1.32%)  1/69 (1.45%) 
Ileal perforation  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Ileus  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Incarcerated inguinal hernia  1  2/73 (2.74%)  0/76 (0.00%)  0/69 (0.00%) 
Inguinal hernia  1  1/73 (1.37%)  2/76 (2.63%)  0/69 (0.00%) 
Necrotising colitis  1  0/73 (0.00%)  3/76 (3.95%)  0/69 (0.00%) 
Vomiting  1  0/73 (0.00%)  1/76 (1.32%)  2/69 (2.90%) 
General disorders       
Cyst  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
No adverse event  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Hepatobiliary disorders       
Hepatic failure  1  0/73 (0.00%)  1/76 (1.32%)  1/69 (1.45%) 
Infections and infestations       
Bronchiolitis  1  2/73 (2.74%)  4/76 (5.26%)  0/69 (0.00%) 
Bronchitis  1  1/73 (1.37%)  0/76 (0.00%)  1/69 (1.45%) 
Conjunctivitis  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Cytomegalovirus infection  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Endophthalmitis  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Enterococcal sepsis  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Escherichia urinary tract infection  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Gastroenteritis  1  1/73 (1.37%)  0/76 (0.00%)  1/69 (1.45%) 
Klebsiella sepsis  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Lower respiratory tract infection viral  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Nasopharyngitis  1  0/73 (0.00%)  2/76 (2.63%)  0/69 (0.00%) 
Orbital infection  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Peritonitis  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Pneumonia  1  4/73 (5.48%)  0/76 (0.00%)  2/69 (2.90%) 
Pneumonia bacterial  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Pneumonia respiratory syncytial viral  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Pneumonia staphylococcal  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Respiratory syncytial virus bronchiolitis  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Respiratory tract infection  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Rhinovirus infection  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Roseola  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Sepsis  1  0/73 (0.00%)  1/76 (1.32%)  2/69 (2.90%) 
Septic shock  1  1/73 (1.37%)  1/76 (1.32%)  0/69 (0.00%) 
Staphylococcal infection  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Staphylococcal sepsis  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Upper respiratory tract infection  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Urinary tract infection  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Viral infection  1  1/73 (1.37%)  1/76 (1.32%)  1/69 (1.45%) 
Injury, poisoning and procedural complications       
Gastrointestinal stoma complication  1  1/73 (1.37%)  0/76 (0.00%)  1/69 (1.45%) 
Greenstick fracture  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Investigations       
Blood potassium increased  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Oxygen saturation decreased  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Weight decreased  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Metabolism and nutrition disorders       
Dehydration  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Failure to thrive  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Hypernatraemia  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Hyperphosphatasaemia  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Musculoskeletal and connective tissue disorders       
Bone disorder  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Osteopenia  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Haemangioma  1  1/73 (1.37%)  1/76 (1.32%)  0/69 (0.00%) 
Nervous system disorders       
Brain oedema  1  2/73 (2.74%)  0/76 (0.00%)  0/69 (0.00%) 
Cerebellar haemorrhage  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Cerebral cyst  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Cognitive disorder  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Hydrocephalus  1  1/73 (1.37%)  0/76 (0.00%)  1/69 (1.45%) 
Nystagmus  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Partial seizures  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Pregnancy, puerperium and perinatal conditions       
Perinatal brain damage  1  0/73 (0.00%)  0/76 (0.00%)  2/69 (2.90%) 
Psychiatric disorders       
Breath holding  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Psychomotor retardation  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Renal and urinary disorders       
Renal failure  1  0/73 (0.00%)  1/76 (1.32%)  1/69 (1.45%) 
Tubulointerstitial nephritis  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Respiratory, thoracic and mediastinal disorders       
Apnoea  1  0/73 (0.00%)  2/76 (2.63%)  2/69 (2.90%) 
Aspiration  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Atelectasis  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Bronchopulmonary dysplasia  1  2/73 (2.74%)  2/76 (2.63%)  2/69 (2.90%) 
Cough  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Dyspnoea  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Pneumonia aspiration  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Pulmonary hypertension  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Pulmonary vein stenosis  1  0/73 (0.00%)  1/76 (1.32%)  1/69 (1.45%) 
Respiratory arrest  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Respiratory distress  1  1/73 (1.37%)  1/76 (1.32%)  0/69 (0.00%) 
Respiratory failure  1  0/73 (0.00%)  3/76 (3.95%)  1/69 (1.45%) 
Respiratory symptom  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Tracheomalacia  1  0/73 (0.00%)  1/76 (1.32%)  0/69 (0.00%) 
Wheezing  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
Skin and subcutaneous tissue disorders       
Purpura  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Social circumstances       
Dependence on oxygen therapy  1  1/73 (1.37%)  0/76 (0.00%)  0/69 (0.00%) 
Vascular disorders       
Haemodynamic instability  1  0/73 (0.00%)  0/76 (0.00%)  1/69 (1.45%) 
1
Term from vocabulary, MedDRA (20.1)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
Ranibizumab 0.2 mg Ranibizumab 0.1 mg Laser
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   43/73 (58.90%)   47/76 (61.84%)   37/69 (53.62%) 
Blood and lymphatic system disorders       
Anaemia  1  4/73 (5.48%)  8/76 (10.53%)  5/69 (7.25%) 
Anaemia neonatal  1  2/73 (2.74%)  4/76 (5.26%)  1/69 (1.45%) 
Cardiac disorders       
Bradycardia  1  2/73 (2.74%)  5/76 (6.58%)  1/69 (1.45%) 
Eye disorders       
Conjunctival haemorrhage  1  6/73 (8.22%)  6/76 (7.89%)  2/69 (2.90%) 
Retinal haemorrhage  1  6/73 (8.22%)  10/76 (13.16%)  7/69 (10.14%) 
Vitreous haemorrhage  1  0/73 (0.00%)  4/76 (5.26%)  0/69 (0.00%) 
Gastrointestinal disorders       
Diarrhoea  1  4/73 (5.48%)  0/76 (0.00%)  1/69 (1.45%) 
Gastrooesophageal reflux disease  1  5/73 (6.85%)  5/76 (6.58%)  4/69 (5.80%) 
Inguinal hernia  1  3/73 (4.11%)  0/76 (0.00%)  2/69 (2.90%) 
Vomiting  1  2/73 (2.74%)  4/76 (5.26%)  2/69 (2.90%) 
General disorders       
Pyrexia  1  9/73 (12.33%)  6/76 (7.89%)  4/69 (5.80%) 
Infections and infestations       
Conjunctivitis  1  1/73 (1.37%)  6/76 (7.89%)  2/69 (2.90%) 
Nasopharyngitis  1  7/73 (9.59%)  5/76 (6.58%)  4/69 (5.80%) 
Pneumonia  1  1/73 (1.37%)  1/76 (1.32%)  6/69 (8.70%) 
Rhinitis  1  3/73 (4.11%)  0/76 (0.00%)  2/69 (2.90%) 
Sepsis  1  1/73 (1.37%)  0/76 (0.00%)  3/69 (4.35%) 
Upper respiratory tract infection  1  6/73 (8.22%)  3/76 (3.95%)  1/69 (1.45%) 
Urinary tract infection  1  3/73 (4.11%)  2/76 (2.63%)  2/69 (2.90%) 
Musculoskeletal and connective tissue disorders       
Osteopenia  1  0/73 (0.00%)  4/76 (5.26%)  1/69 (1.45%) 
Respiratory, thoracic and mediastinal disorders       
Apnoea  1  1/73 (1.37%)  4/76 (5.26%)  1/69 (1.45%) 
Bronchopulmonary dysplasia  1  2/73 (2.74%)  3/76 (3.95%)  4/69 (5.80%) 
Bronchospasm  1  3/73 (4.11%)  0/76 (0.00%)  1/69 (1.45%) 
Cough  1  4/73 (5.48%)  2/76 (2.63%)  1/69 (1.45%) 
Skin and subcutaneous tissue disorders       
Dermatitis diaper  1  8/73 (10.96%)  6/76 (7.89%)  4/69 (5.80%) 
1
Term from vocabulary, MedDRA (20.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02375971     History of Changes
Other Study ID Numbers: CRFB002H2301
2014-003041-10 ( EudraCT Number )
First Submitted: February 18, 2015
First Posted: March 3, 2015
Results First Submitted: June 5, 2018
Results First Posted: July 31, 2018
Last Update Posted: November 14, 2018