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Retinopathy of PrematurityPhase 3RAINBOWNCT02375971

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

A Phase 3 study testing Ranibizumab and Laser therapy in people with Retinopathy of Prematurity, run by Novartis Pharmaceuticals at 86 sites in 26 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Any age
Conditions the study is for
Retinopathy of Prematurity
What is being tested?
Ranibizumab and Laser therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
224 participants
Where
86 sitesin 26 countries
Study dates
30 Dec 2015to 14 Dec 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 10Show fewer
  • 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)

Trial locations and contacts

86 sites in 26 countries.

86 sites in 26 countries

Japan17 sites

  • Novartis Investigative Site

    Fuchū, Tokyo, 183-8561

  • Novartis Investigative Site

    Fukuoka, Fukuoka, 812-8582

  • Novartis Investigative Site

    Fukuoka, Fukuoka, 814-0180

  • Novartis Investigative Site

    Fukushima, Fukushima, 960-1295

  • Novartis Investigative Site

    Izumi, Osaka, 594-1101

  • Novartis Investigative Site

    Kurume, Fukuoka, 830-0011

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 453-8511

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 466 8560

  • Novartis Investigative Site

    Ohtsu-city, Shiga, 520-2192

  • Novartis Investigative Site

    Ōta-ku, Tokyo, 143 8541

  • Novartis Investigative Site

    Sapporo, Hokkaido

  • Novartis Investigative Site

    Setagaya-ku, Tokyo, 157-8535

  • Novartis Investigative Site

    Shimajiri-Gun, Okinawa, 901-1303

  • Novartis Investigative Site

    Sumida-ku, Tokyo, 130-8575

  • Novartis Investigative Site

    Toshima-ku, Tokyo, 170-8476

  • Novartis Investigative Site

    Yachiyo, Chiba, 276-8524

  • Novartis Investigative Site

    Zentsujichó, Kagawa-ken, 765-8507

Other trials in Japan

United States12 sites

  • Novartis Investigative Site

    Ann Arbor, Michigan, 48105

  • Novartis Investigative Site

    Aurora, Colorado, 80045

  • Novartis Investigative Site

    Austin, Texas, 78705

  • Novartis Investigative Site

    Baltimore, Maryland, 21201

  • Novartis Investigative Site

    Boston, Massachusetts, 02111

  • Novartis Investigative Site

    Chicago, Illinois, 60612

  • Novartis Investigative Site

    Loma Linda, California, 92354

  • Novartis Investigative Site

    Louisville, Kentucky, 40208

  • Novartis Investigative Site

    Morgantown, West Virginia, 26506

  • Novartis Investigative Site

    Rochester, New York, 14642

  • Novartis Investigative Site

    Sacramento, California, 95817

  • Novartis Investigative Site

    Salt Lake City, Utah, 84132

Other trials in United States

India6 sites

  • Novartis Investigative Site

    Ahmedabad, Gujarat, 380016

  • Novartis Investigative Site

    Coimbatore, Tamil Nadu, 641014

  • Novartis Investigative Site

    Madurai, Tamil Nadu, 625020

  • Novartis Investigative Site

    Mumbai, Maharashtra, 400 008

  • Novartis Investigative Site

    New Delhi, 110029

  • Novartis Investigative Site

    Vanchiyoor, Thiruvanantapuram, 695035

Other trials in India

Turkey (Türkiye)6 sites

  • Novartis Investigative Site

    Ankara, 06100

  • Novartis Investigative Site

    Ankara, 06500

  • Novartis Investigative Site

    Eskişehir, Meselik, 26480

  • Novartis Investigative Site

    Istanbul, 34140

  • Novartis Investigative Site

    Soguksu / Antalya, Turkey, 07100

  • Novartis Investigative Site

    Zuhuratbaba / Istanbul, Turkey, 34147

Other trials in Turkey (Türkiye)

Italy4 sites

  • Novartis Investigative Site

    Fiumicino, RM, 00054

  • Novartis Investigative Site

    Florence, FI, 50139

  • Novartis Investigative Site

    Perugia, PG, 06100

  • Novartis Investigative Site

    Rome, Lazio, 00168

Other trials in Italy

Russia4 sites

  • Novartis Investigative Site

    Cheboksary, 428028

  • Novartis Investigative Site

    Kazan', 420012

  • Novartis Investigative Site

    Moscow, 127486

  • Novartis Investigative Site

    Saint Petersburg, 194100

Other trials in Russia

Czechia3 sites

  • Novartis Investigative Site

    Ostrava Poruba, Czech Republic, 708 52

  • Novartis Investigative Site

    Prague, 12808

  • Novartis Investigative Site

    Praha 4 - Podoli, Czech Republic, 14700

Other trials in Czechia

Greece3 sites

  • Novartis Investigative Site

    Ampelokipoi, GR, 115 27

  • Novartis Investigative Site

    Goudi- Athens, 115 27

  • Novartis Investigative Site

    Thessaloniki, GR, 546 29

Other trials in Greece

Romania3 sites

  • Novartis Investigative Site

    Brasov, 500025

  • Novartis Investigative Site

    Bucharest, 020395

  • Novartis Investigative Site

    Timișoara, 300041

Other trials in Romania

United Kingdom3 sites

  • Novartis Investigative Site

    Manchester, M13 9WL

  • Novartis Investigative Site

    Oxford, OX3 9DU

  • Novartis Investigative Site

    Portsmouth, PO6 3LY

Other trials in United Kingdom

Austria2 sites

  • Novartis Investigative Site

    Graz, A-8036

  • Novartis Investigative Site

    Vienna, 1090

Other trials in Austria

Belgium2 sites

  • Novartis Investigative Site

    Bruges, 8000

  • Novartis Investigative Site

    Ghent, 9000

Other trials in Belgium

Croatia2 sites

  • Novartis Investigative Site

    Osijek, 31000

  • Novartis Investigative Site

    Zagreb, 10000

Other trials in Croatia

France2 sites

  • Novartis Investigative Site

    Amiens, 80054

  • Novartis Investigative Site

    Marseille, 13915

Other trials in France

Germany2 sites

  • Novartis Investigative Site

    Bonn, 53127

  • Novartis Investigative Site

    Hanover, 30625

Other trials in Germany

Hungary2 sites

  • Novartis Investigative Site

    Budapest, 1125

  • Novartis Investigative Site

    Debrecen, 4032

Other trials in Hungary

Malaysia2 sites

  • Novartis Investigative Site

    Kota Kinabalu, Sabah, 88996

  • Novartis Investigative Site

    Kuala Lumpur, Kuala Lumpur, 50586

Other trials in Malaysia

Poland2 sites

  • Novartis Investigative Site

    Bialystok, 15-274

  • Novartis Investigative Site

    Wroclaw, 51-124

Other trials in Poland

Taiwan2 sites

  • Novartis Investigative Site

    Taipei, 10002

  • Novartis Investigative Site

    Taoyuan, 33305

Other trials in Taiwan

Denmark1 site

  • Novartis Investigative Site

    Koebenhavn Ø, 2100

Other trials in Denmark

Egypt1 site

  • Novartis Investigative Site

    Alexandria, 21131

Other trials in Egypt

Estonia1 site

  • Novartis Investigative Site

    Tallinn, 13419

Other trials in Estonia

Lithuania1 site

  • Novartis Investigative Site

    Kaunas, LTU, LT-50161

Other trials in Lithuania

Mexico1 site

  • Novartis Investigative Site

    Querataro, 76090

Other trials in Mexico

Saudi Arabia1 site

  • Novartis Investigative Site

    Riyadh, 11211

Other trials in Saudi Arabia

Slovakia1 site

  • Novartis Investigative Site

    Bratislava, 833 40

Other trials in Slovakia

About this study

Official title: 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

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).

Read the 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).

Being tested
Ranibizumab, Laser therapy
Keywords
intravitreal ranibizumab, laser ablation therapy, retinopathy of prematurity, preterm infants, RAINBOW
Medical subject headings
Retinopathy of Prematurity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RanibizumabDrug

    Administered as an intravitreal injection

  • Laser therapyProcedure or surgery

    Transpupillary diode or frequency-doubled yttrium aluminum garnet (YAG) laser ablative therapy, following anesthesia or sedation

Study groups in NCT02375971
Study groupRoleWhat they receive
Ranibizumab 0.2 mgExperimental1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
Receives: Drug: Ranibizumab
Ranibizumab 0.1 mgExperimental1 intravitreal injection in both eyes on Day 1 (Baseline), with up to 2 re-treatments allowed for each eye if required
Receives: Drug: Ranibizumab
Laser therapyActive comparatorLaser treatment to each eye on Day 1 (Baseline), with supplementary treatments allowed
Receives: Procedure: Laser therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Absence of Active ROP and Absence of Unfavorable Structural Outcomes in Both Eyes at 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.

    Measured: Week 24

Secondary outcomes (11)

  1. Percentage of Participants Requiring Interventions With a Second Modality for ROP at 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.

    Measured: Week 24

  2. Number of Participants Experiencing an Event, From the First Study Treatment to the Last Study Visit

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

    Measured: Day 1 (after initiation of study treatment) up to study exit (Day 169)

  3. Percentage of Participants Having Recurrent ROP and Receiving Any Post-baseline Intervention at or Before 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.

    Measured: Week 24

  4. Percent of Participants With Ocular Adverse Events by Primary System Organ (SOCs) at 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.

    Measured: Week 24

  5. Mean Change in Ranibizumab Concentration in Pharmacokinetic Serum Samples Over Time at Day 1, 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.

    Measured: Day 1 (Baseline), Day 15 and Day 29

  6. Mean Change in Vascular Endothelial Growth Factor (VEGF) Levels Over Time at Day 1, 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.

    Measured: Day 1 (Baseline), Day 15 and Day 29

  7. Total Number of Ranibizumab Injections Received at 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.

    Measured: Week 24

  8. Percent of Participants With Non-Ocular Adverse Events by Primary System Organ (SOCs) at 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.

    Measured: Week 24

  9. Mean Change From Baseline in Vital Signs (Body Length, Head Circumference and Knee to Heel Length) at Day 85 and Day 169

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

    Measured: Baseline, Day 85, Day 169

  10. Mean Change From Baseline in Vital Signs (Weight) at Day 85 and Day 169

    Body weight was measured. Only descriptive analysis done.

    Measured: Baseline, Day 85, Day 169

  11. Mean Change From Baseline in Vital Signs (Sitting Blood Pressure) at Day 85 and 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.

    Measured: Baseline, Day 85, Day 169

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Mar 2015 (estimated)
  2. Study start30 Dec 2015
  3. Primary completion14 Dec 2017
  4. Study completion14 Dec 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
224 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02375971
Sponsor's protocol ID
CRFB002H2301
Other IDs
2014-003041-10, 2014
Acronym
RAINBOW
Status last verified
Oct 2018
First submitted
18 Feb 2015
Last updated
14 Nov 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: 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.

Publications

  • Fleck BW, Reynolds JD, Zhu Q, Lepore D, Marlow N, Stahl A, Li J, Weisberger A, Fielder AR; RAINBOW Investigator Group. Time Course of Retinopathy of Prematurity Regression and Reactivation After Treatment with Ranibizumab or Laser in the RAINBOW Trial. Ophthalmol Retina. 2022 Jul;6(7):628-637. doi: 10.1016/j.oret.2022.02.006. Epub 2022 Feb 22.

    PubMed 35202890

  • Stahl A, Lepore D, Fielder A, Fleck B, Reynolds JD, Chiang MF, Li J, Liew M, Maier R, Zhu Q, Marlow N. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial. Lancet. 2019 Oct 26;394(10208):1551-1559. doi: 10.1016/S0140-6736(19)31344-3. Epub 2019 Sep 12.

    PubMed 31522845

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ranibizumab and Laser therapy in people with Retinopathy of Prematurity, run by Novartis Pharmaceuticals at 86 sites in 26 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 86 sites in Japan, United States, India, Turkey (Türkiye), Italy and 21 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Absence of Active ROP and Absence of Unfavorable Structural Outcomes in Both Eyes at Week 24 (time frame: Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02375971, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2018.

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