A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Diabetes Mellitus (RISE)

A Phase 3 study testing Ranibizumab in people with Diabetes Mellitus and Macular Edema, run by Genentech, Inc..

Completed

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

Trial summary

This study is a Phase III, double-masked, multicenter, randomized, sham injection-controlled study of the efficacy and safety of ranibizumab injection in patients with clinically significant macular edema with center involvement (CSME-CI) secondary to diabetes mellitus (Type 1 or 2). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Diabetes Mellitus, Macular Edema
What is being tested?: Ranibizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 377 participants
Where: No sites listed yet
Study dates: Jun 2007to Nov 2012
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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Willingness to provide written informed consent and, at U.S. sites, Health Insurance Portability and Accountability Act (HIPAA) authorization, and in other countries, as applicable according to national laws.
Age ≥ 18 years.
Diabetes mellitus (Type 1 or 2) .
Retinal thickening secondary to diabetes mellitus (DME) involving the center of the fovea with central macular thickness ≥ 275 µm in the center subfield as assessed on optical coherence tomography (OCT).
Best corrected visual acuity (BCVA) score in the study eye of 20/40 to 20/320 approximate Snellen equivalent using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at an initial testing distance of 4 meters.
Decrease in vision determined to be primarily the result of DME and not to other causes.
For sexually active women of childbearing potential, use of an appropriate form of contraception (or abstinence) for the duration of the study.
Ability (in the opinion of the investigator) and willingness to return for all scheduled visits and assessments.

Who cannot join

History of vitreoretinal surgery in the study eye.
Panretinal photocoagulation (PRP) or macular laser photocoagulation in the study eye within 3 months of screening.
Previous use of intraocular corticosteroids in the study eye (eg, triamcinolone acetonide [TA]) within 3 months of screening.
Previous treatment with anti-angiogenic drugs in either eye (pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, etc) within 3 months of the Day 0 (first day of treatment) visit.
Proliferative diabetic retinopathy (PDR) in the study eye, with the exception of inactive, regressed PDR.
Iris neovascularization, vitreous hemorrhage, traction retinal detachment, or preretinal fibrosis involving the macula in the study eye.

Show all 27Show fewer

Concurrent Ocular Conditions
Vitreomacular traction or epiretinal membrane in the study eye.
Ocular inflammation (including trace or above) in the study eye.
History of idiopathic or autoimmune uveitis in either eye.
Structural damage to the center of the macula in the study eye that is likely to preclude improvement in VA following the resolution of macular edema, including atrophy of the retinal pigment epithelium (RPE), subretinal fibrosis, or organized hard-exudate plaque.
Ocular disorders in the study eye that may confound interpretation of study results, including retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization (CNV) of any cause (eg, age-related macular degeneration (AMD), ocular histoplasmosis, or pathologic myopia).
Concurrent disease in the study eye that would compromise visual acuity or require medical or surgical intervention during the study period.
Cataract surgery in the study eye within 3 months, yttrium-aluminum-garnet (YAG) laser capsulotomy within the past 2 months, or any other intraocular surgery within the 90 days preceding Day 0.
Aphakia or absence of the posterior capsule in the study eye.
Uncontrolled glaucoma or previous filtration surgery in the study eye.
Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia.
Evidence at examination of infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye or current treatment for serious systemic infection.
Uncontrolled blood pressure.
History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0.
Uncontrolled diabetes mellitus.
Renal failure requiring dialysis or renal transplant.
Participation in an investigational trial within 30 days prior to screening that involved treatment with any drug (excluding vitamins and minerals) or device.
History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug, might affect interpretation of the results of the study, or renders the subject at high risk from treatment complications.
Pregnancy or lactation.
History of allergy to fluorescein.
History of allergy to ranibizumab injection or related molecule.

About this study

Official title: A Phase III, Double-masked, Multicenter, Randomized, Sham Injection-controlled Study of the Efficacy and Safety of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema With Center Involvement Secondary to Diabetes Mellitus

The open-label extension phase of the study was stopped after receiving FDA approval of the study drug (ranibizumab) for diabetic macular edema.

Read the detailed description

This study is composed of 3 phases: (1) A 24-month controlled treatment period (monthly treatment with ranibizumab 0.3 mg, ranibizumab 0.5 mg, or sham injection) followed by (2) a 12-month treatment period in which patients randomized to the sham group who had not discontinued from treatment (still masked) could choose to receive monthly ranibizumab 0.5 mg while the 2 ranibizumab treatment groups continued on the same treatment they received in the first 2 years. Patients who had not discontinued treatment by Month 36 were eligible to continue treatment with ranibizumab 0.5 mg as needed (pro re nata, PRN) in (3) an extension phase of the study for up to 2 more years, resulting in up to 5 years possible total treatment time for some patients.

Conditions: Diabetes Mellitus, Macular Edema
Being tested: Ranibizumab, Sham injection
Keywords: Lucentis, DME, Diabetes, Vision loss
Medical subject headings: Diabetes Mellitus, Macular Edema, Vision Disorders

What participants receive

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

RanibizumabDrug
Also called Lucentis
Sterile solution for intravitreal injection.
Sham injectionDrug

Study groups in NCT00473330
Study group	Role	What they receive
Ranibizumab 0.3 mg	Experimental	Patients received ranibizumab 0.3 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. Receives: Drug: Ranibizumab
Ranibizumab 0.5 mg	Experimental	Patients received ranibizumab 0.5 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. Receives: Drug: Ranibizumab
Sham injection/ranibizumab 0.5 mg	Sham comparator	Patients received a sham intravitreal injection monthly for 24 months. Patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. Receives: Drug: Sham injection

What is being measured

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

Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Month 24
BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision.
Measured: Baseline to Month 24

Secondary outcomes (12)

Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Months 24, 36, and 48
BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A positive change score indicates improvement.
Measured: Baseline to Month 48
Percentage of Patients With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better at Months 24, 36, and 48
VA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart starting at a test distance of 4 meters. An increase in the number of lines read correctly by the patient in the ETDRS chart indicates an improvement of vision. The Snellen equivalent of 20/40 or better is 69 or more letters correctly read in the EDTRS chart.
Measured: Months 24, 36, and 48
Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Months 24, 36, and 48
BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision.
Measured: Baseline to Month 48
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Months 24 and 36 in Patients With Focal Edema at Baseline
BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A positive change score indicates improvement.
Measured: Baseline to Month 36
Mean Change From Baseline in Central Foveal Thickness at Months 24, 36, and 48
Central foveal thickness was assessed in optical coherence tomographic images by the central reading center. A decrease in foveal thickness suggests a reduction in macular edema. A negative change score indicates improvement.
Measured: Baseline to Month 48
Percentage of Patients With a ≥ 3-step Worsening From Baseline in the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale Score for Eyes at Months 24 and 36
The severity of diabetic retinopathy was graded on a 10-point scale by the central reading center by comparing patient fundus photographic images with a set of standard images. 1=diabetic retinopathy (DR) severity level 10, 12 (DR absent), 2=DR severity level 14A-14C, 14Z, 15, 20 (DR questionable, microaneurysms only), 3=DR severity level 35A-35F (mild non-proliferative [NP]DR), 4=DR severity level 43A, 43B (moderate NPDR), 5=DR severity level 47A-47D (moderately severe NPDR), 6=DR severity level 53A-53E (severe NPDR), 7=DR severity level 60, 61A, 61B (mild proliferative [P]DR), 8=DR severity level 65A-65C (moderate PDR), 9=DR severity level 71A-71D (high-risk PDR), 10=DR severity level 90 (cannot grade). A lower score indicates less severe diabetic retinopathy.
Measured: Baseline to Month 36
Percentage of Patients With Resolution of Leakage at Month 24
Resolution of leakage was defined as total area of fluorescein leakage in the central, inner, and outer subfields of the 0 Disc Area. Leakage was assessed in fluorescein angiographic images by the central reading center.
Measured: Baseline to Month 24
Mean Number of Macular Laser Treatments From Baseline Through Months 24 and 36
The need for macular laser treatment was evaluated by the masked (evaluating) physician. Macular laser was administered per protocol-specified objective and subjective criteria starting at Month 3.
Measured: Baseline to Month 36
Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Months 36 and 48
BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision.
Measured: Baseline to Month 48
Mean Change From Month 36 in Best Corrected Visual Acuity (BCVA) Score in the Study Eye at Month 48
BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A positive change score indicates improvement.
Measured: Month 36 to Month 48
Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score in the Study Eye From Month 36 at Month 48
BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision.
Measured: Month 36 to Month 48
Mean Change From Month 36 in Central Foveal Thickness in the Study Eye at Month 48
Central foveal thickness was assessed in optical coherence tomographic images by the central reading center. A decrease in foveal thickness suggests a reduction in macular edema. A negative change score indicates improvement.
Measured: Month 36 to Month 48

Timeline

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

Jun 2007Nov 2012

First posted15 May 2007 (estimated)
Study startJun 2007
Primary completionNov 2010
Study completionNov 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (19)Papers the sponsor has linked to this study.
Other trials for Diabetes MellitusStudies of the same condition, open and under way.
More trials run by Genentech, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Double blind
Who is masked: Participant, Investigator
Enrolment: 377 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00473330
Sponsor's protocol ID: FVF4170g
Acronym: RISE
Status last verified: Mar 2017
First submitted: 13 May 2007
Last updated: 17 Apr 2017
Results posted: Yes, on ClinicalTrials.gov

Publications

Bressler N, Haskova Z, Kapre A, Gentile B. Clinically Meaningful Change Estimates for the National Eye Institute Visual Function Questionnaire-25 in Patients With Diabetic Macular Edema. Transl Vis Sci Technol. 2024 Dec 2;13(12):27. doi: 10.1167/tvst.13.12.27.
PubMed 39680390
Stockwell AD, Chang MC, Mahajan A, Forrest W, Anegondi N, Pendergrass RK, Selvaraj S, Reeder J, Wei E, Iglesias VA, Creps NM, Macri L, Neeranjan AN, van der Brug MP, Scales SJ, McCarthy MI, Yaspan BL. Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema. PLoS Genet. 2023 Aug 16;19(8):e1010609. doi: 10.1371/journal.pgen.1010609. eCollection 2023 Aug.
PubMed 37585454
Talcott KE, Valentim CCS, Hill L, Stoilov I, Singh RP. Baseline Diabetic Retinopathy Severity and Time to Diabetic Macular Edema Resolution with Ranibizumab Treatment: A Meta-Analysis. Ophthalmol Retina. 2023 Jul;7(7):605-611. doi: 10.1016/j.oret.2023.02.003. Epub 2023 Feb 10.
PubMed 36774994
Goldberg RA, Hill L, Davis T, Stoilov I. Effect of less aggressive treatment on diabetic retinopathy severity scale scores: analyses of the RIDE and RISE open-label extension. BMJ Open Ophthalmol. 2022 Jul;7(1):e001007. doi: 10.1136/bmjophth-2022-001007.
PubMed 36161830
Singer M, Liu M, Schlottmann PG, Khanani AM, Hemphill M, Hill L, Tuomi L, Haskova Z. Predictors of Early Diabetic Retinopathy Regression with Ranibizumab in the RIDE and RISE Clinical Trials. Clin Ophthalmol. 2020 Jun 17;14:1629-1639. doi: 10.2147/OPTH.S247061. eCollection 2020.
PubMed 32606578
Gonzalez VH, Wang PW, Ruiz CQ. Panretinal Photocoagulation for Diabetic Retinopathy in the RIDE and RISE Trials: Not "1 and Done". Ophthalmology. 2021 Oct;128(10):1448-1457. doi: 10.1016/j.ophtha.2019.08.010. Epub 2019 Aug 21.
PubMed 31668888
Wykoff CC, Eichenbaum DA, Roth DB, Hill L, Fung AE, Haskova Z. Ranibizumab Induces Regression of Diabetic Retinopathy in Most Patients at High Risk of Progression to Proliferative Diabetic Retinopathy. Ophthalmol Retina. 2018 Oct;2(10):997-1009. doi: 10.1016/j.oret.2018.06.005. Epub 2018 Aug 1.
PubMed 31047503
Moshfeghi AA, Shapiro H, Lemmon LA, Gune S. Impact of Cataract Surgery during Treatment with Ranibizumab in Patients with Diabetic Macular Edema. Ophthalmol Retina. 2018 Feb;2(2):86-90. doi: 10.1016/j.oret.2017.05.003. Epub 2017 Jul 27.
PubMed 31047350
Sun JK, Wang PW, Taylor S, Haskova Z. Durability of Diabetic Retinopathy Improvement with As-Needed Ranibizumab: Open-Label Extension of RIDE and RISE Studies. Ophthalmology. 2019 May;126(5):712-720. doi: 10.1016/j.ophtha.2018.10.041. Epub 2018 Nov 9.
PubMed 30419298
Reddy RK, Pieramici DJ, Gune S, Ghanekar A, Lu N, Quezada-Ruiz C, Baumal CR. Efficacy of Ranibizumab in Eyes with Diabetic Macular Edema and Macular Nonperfusion in RIDE and RISE. Ophthalmology. 2018 Oct;125(10):1568-1574. doi: 10.1016/j.ophtha.2018.04.002. Epub 2018 May 8.
PubMed 29752001
Singh RP, Habbu K, Ehlers JP, Lansang MC, Hill L, Stoilov I. The Impact of Systemic Factors on Clinical Response to Ranibizumab for Diabetic Macular Edema. Ophthalmology. 2016 Jul;123(7):1581-7. doi: 10.1016/j.ophtha.2016.03.038. Epub 2016 May 24.
PubMed 27234930
Pieramici DJ, Wang PW, Ding B, Gune S. Visual and Anatomic Outcomes in Patients with Diabetic Macular Edema with Limited Initial Anatomic Response to Ranibizumab in RIDE and RISE. Ophthalmology. 2016 Jun;123(6):1345-50. doi: 10.1016/j.ophtha.2016.02.007. Epub 2016 Mar 15.
PubMed 26992841
Bressler NM, Varma R, Mitchell P, Suner IJ, Dolan C, Ward J, Ferreira A, Ehrlich JS, Turpcu A. Effect of Ranibizumab on the Decision to Drive and Vision Function Relevant to Driving in Patients With Diabetic Macular Edema: Report From RESTORE, RIDE, and RISE Trials. JAMA Ophthalmol. 2016 Feb;134(2):160-6. doi: 10.1001/jamaophthalmol.2015.4636.
PubMed 26584450
Boyer DS, Nguyen QD, Brown DM, Basu K, Ehrlich JS; RIDE and RISE Research Group. Outcomes with As-Needed Ranibizumab after Initial Monthly Therapy: Long-Term Outcomes of the Phase III RIDE and RISE Trials. Ophthalmology. 2015 Dec;122(12):2504-13.e1. doi: 10.1016/j.ophtha.2015.08.006. Epub 2015 Oct 9.
PubMed 26452713
Bansal AS, Khurana RN, Wieland MR, Wang PW, Van Everen SA, Tuomi L. Influence of Glycosylated Hemoglobin on the Efficacy of Ranibizumab for Diabetic Macular Edema: A Post Hoc Analysis of the RIDE/RISE Trials. Ophthalmology. 2015 Aug;122(8):1573-9. doi: 10.1016/j.ophtha.2015.04.029. Epub 2015 Jun 4.
PubMed 26050541

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Recruiting
Effects of Lean Pork Loin Intake on Protein Homeostasis and Glucose Regulation in Prediabetic Adults
Hyperglycaemia (Non Diabetic), Prediabetes
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)

All Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Double-masked, Multicenter, Randomized, Sham Injection-controlled Study of the Efficacy and Safety of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema With Center Involvement Secondary to Diabetes Mellitus
ClinicalTrials.gov ID: NCT00473330
Acronym / sponsor ID: RISE / FVF4170g
Conditions: Diabetes Mellitus, Macular Edema
Keywords: Lucentis, DME, Diabetes, Vision loss
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 377 participants (actual)
Lead sponsor: Genentech, Inc.Industry (pharma, biotech, devices)
Study start: Jun 2007
Primary completion: Nov 2010 (actual)
Study completion: Nov 2012 (actual)
First posted: 15 May 2007 (estimated)
Results: Posted 17 Jan 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The open-label extension phase of the study was stopped after receiving FDA approval of the study drug (ranibizumab) for diabetic macular edema.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Ranibizumab 0.3 mg	Experimental	Drug: RanibizumabPatients received ranibizumab 0.3 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months.
Ranibizumab 0.5 mg	Experimental	Drug: RanibizumabPatients received ranibizumab 0.5 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months.
Sham injection/ranibizumab 0.5 mg	Sham comparator	Drug: Sham injectionPatients received a sham intravitreal injection monthly for 24 months. Patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Willingness to provide written informed consent and, at U.S. sites, Health Insurance Portability and Accountability Act (HIPAA) authorization, and in other countries, as applicable according to national laws.
Age ≥ 18 years.
Diabetes mellitus (Type 1 or 2) .
Retinal thickening secondary to diabetes mellitus (DME) involving the center of the fovea with central macular thickness ≥ 275 µm in the center subfield as assessed on optical coherence tomography (OCT).
Best corrected visual acuity (BCVA) score in the study eye of 20/40 to 20/320 approximate Snellen equivalent using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at an initial testing distance of 4 meters.

Key exclusion criteria (27 listed)

History of vitreoretinal surgery in the study eye.
Panretinal photocoagulation (PRP) or macular laser photocoagulation in the study eye within 3 months of screening.
Previous use of intraocular corticosteroids in the study eye (eg, triamcinolone acetonide [TA]) within 3 months of screening.
Previous treatment with anti-angiogenic drugs in either eye (pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, etc) within 3 months of the Day 0 (first day of treatment) visit.
Proliferative diabetic retinopathy (PDR) in the study eye, with the exception of inactive, regressed PDR.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RanibizumabAlso: LucentisSterile solution for intravitreal injection.	Drug	Ranibizumab 0.3 mg, Ranibizumab 0.5 mg
Sham injection	Drug	Sham injection/ranibizumab 0.5 mg

Primary outcome

Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Month 24
Time frame: Baseline to Month 24
BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision.

12 secondary outcomes

Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Months 24, 36, and 48
Time frame: Baseline to Month 48
Percentage of Patients With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better at Months 24, 36, and 48
Time frame: Months 24, 36, and 48
Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Months 24, 36, and 48
Time frame: Baseline to Month 48
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Months 24 and 36 in Patients With Focal Edema at Baseline
Time frame: Baseline to Month 36
Mean Change From Baseline in Central Foveal Thickness at Months 24, 36, and 48
Time frame: Baseline to Month 48
Percentage of Patients With a ≥ 3-step Worsening From Baseline in the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale Score for Eyes at Months 24 and 36
Time frame: Baseline to Month 36
Percentage of Patients With Resolution of Leakage at Month 24
Time frame: Baseline to Month 24
Mean Number of Macular Laser Treatments From Baseline Through Months 24 and 36
Time frame: Baseline to Month 36
Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Months 36 and 48
Time frame: Baseline to Month 48
Mean Change From Month 36 in Best Corrected Visual Acuity (BCVA) Score in the Study Eye at Month 48
Time frame: Month 36 to Month 48
Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score in the Study Eye From Month 36 at Month 48
Time frame: Month 36 to Month 48
Mean Change From Month 36 in Central Foveal Thickness in the Study Eye at Month 48
Time frame: Month 36 to Month 48

Results and safety

Results posted to the registry on 17 Jan 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ranibizumab 0.3 mg	125	98
Ranibizumab 0.5 mg	125	100
Sham Injection/Ranibizumab 0.5 mg	127	86

Primary outcome: Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Month 24

Time frame: Baseline to Month 24. Number (95% Confidence Interval). Unit: Percentage of patients

Measure	Ranibizumab 0.3 mg n = 125	Ranibizumab 0.5 mg n = 125	Sham Injection n = 127
Value	44.8 (36.1 to 53.5)	39.2 (30.6 to 47.8)	18.1 (11.4 to 24.8)

Ranibizumab 0.3 mg vs Sham Injection: Difference in percentage at Month 24: 24.3 (95% CI 13.8 to 34.8), p <0.0001, Cochran-Mantel-Haenszel
Ranibizumab 0.5 mg vs Sham Injection: Difference in percentage at Month 24: 20.9 (95% CI 10.7 to 31.1), p = 0.0002, Cochran-Mantel-Haenszel

Population analysed: Intent-to-treat population: All randomized patients, whether or not treatment was received. Missing data were imputed using the last observation carried forward.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were recorded from the first day of treatment through Month 60. The sham Months 0-36 group includes patients randomized to sham. The sham Months 0-24 group includes patients who received sham during the first 24 months of the study.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sham Injection - Months 0-24	47 of 124 (37.9%)	122 of 124 (98.4%)	Not reported
Sham Injection/Ranibizumab 0.5 mg - Months 0-36	59 of 124 (47.6%)	122 of 124 (98.4%)	Not reported
Ranibizumab 0.3 mg - Months 0-36	60 of 125 (48%)	123 of 125 (98.4%)	Not reported
Ranibizumab 0.5 mg - Months 0-36	69 of 125 (55.2%)	121 of 125 (96.8%)	Not reported
Sham Injection/Ranibizumab 0.5 mg - Months 37-60	18 of 76 (23.7%)	60 of 76 (78.9%)	Not reported
Ranibizumab 0.3 mg - Months 37-60	26 of 90 (28.9%)	76 of 90 (84.4%)	Not reported
Ranibizumab 0.5 mg - Months 37-60	23 of 79 (29.1%)	69 of 79 (87.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39680390Bressler N, Haskova Z, Kapre A, Gentile B. Clinically Meaningful Change Estimates for the National Eye Institute Visual Function Questionnaire-25 in Patients With Diabetic Macular Edema. Transl Vis Sci Technol. 2024 Dec 2;13(12):27. doi: 10.1167/tvst.13.12.27.
Derived from this study: PubMed 37585454Stockwell AD, Chang MC, Mahajan A, Forrest W, Anegondi N, Pendergrass RK, Selvaraj S, Reeder J, Wei E, Iglesias VA, Creps NM, Macri L, Neeranjan AN, van der Brug MP, Scales SJ, McCarthy MI, Yaspan BL. Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema. PLoS Genet. 2023 Aug 16;19(8):e1010609. doi: 10.1371/journal.pgen.1010609. eCollection 2023 Aug.
Derived from this study: PubMed 36774994Talcott KE, Valentim CCS, Hill L, Stoilov I, Singh RP. Baseline Diabetic Retinopathy Severity and Time to Diabetic Macular Edema Resolution with Ranibizumab Treatment: A Meta-Analysis. Ophthalmol Retina. 2023 Jul;7(7):605-611. doi: 10.1016/j.oret.2023.02.003. Epub 2023 Feb 10.
Derived from this study: PubMed 36161830Goldberg RA, Hill L, Davis T, Stoilov I. Effect of less aggressive treatment on diabetic retinopathy severity scale scores: analyses of the RIDE and RISE open-label extension. BMJ Open Ophthalmol. 2022 Jul;7(1):e001007. doi: 10.1136/bmjophth-2022-001007.
Derived from this study: PubMed 32606578Singer M, Liu M, Schlottmann PG, Khanani AM, Hemphill M, Hill L, Tuomi L, Haskova Z. Predictors of Early Diabetic Retinopathy Regression with Ranibizumab in the RIDE and RISE Clinical Trials. Clin Ophthalmol. 2020 Jun 17;14:1629-1639. doi: 10.2147/OPTH.S247061. eCollection 2020.
Derived from this study: PubMed 31668888Gonzalez VH, Wang PW, Ruiz CQ. Panretinal Photocoagulation for Diabetic Retinopathy in the RIDE and RISE Trials: Not "1 and Done". Ophthalmology. 2021 Oct;128(10):1448-1457. doi: 10.1016/j.ophtha.2019.08.010. Epub 2019 Aug 21.
Derived from this study: PubMed 31047503Wykoff CC, Eichenbaum DA, Roth DB, Hill L, Fung AE, Haskova Z. Ranibizumab Induces Regression of Diabetic Retinopathy in Most Patients at High Risk of Progression to Proliferative Diabetic Retinopathy. Ophthalmol Retina. 2018 Oct;2(10):997-1009. doi: 10.1016/j.oret.2018.06.005. Epub 2018 Aug 1.
Derived from this study: PubMed 31047350Moshfeghi AA, Shapiro H, Lemmon LA, Gune S. Impact of Cataract Surgery during Treatment with Ranibizumab in Patients with Diabetic Macular Edema. Ophthalmol Retina. 2018 Feb;2(2):86-90. doi: 10.1016/j.oret.2017.05.003. Epub 2017 Jul 27.
Derived from this study: PubMed 30419298Sun JK, Wang PW, Taylor S, Haskova Z. Durability of Diabetic Retinopathy Improvement with As-Needed Ranibizumab: Open-Label Extension of RIDE and RISE Studies. Ophthalmology. 2019 May;126(5):712-720. doi: 10.1016/j.ophtha.2018.10.041. Epub 2018 Nov 9.
Derived from this study: PubMed 29752001Reddy RK, Pieramici DJ, Gune S, Ghanekar A, Lu N, Quezada-Ruiz C, Baumal CR. Efficacy of Ranibizumab in Eyes with Diabetic Macular Edema and Macular Nonperfusion in RIDE and RISE. Ophthalmology. 2018 Oct;125(10):1568-1574. doi: 10.1016/j.ophtha.2018.04.002. Epub 2018 May 8.
Derived from this study: PubMed 27234930Singh RP, Habbu K, Ehlers JP, Lansang MC, Hill L, Stoilov I. The Impact of Systemic Factors on Clinical Response to Ranibizumab for Diabetic Macular Edema. Ophthalmology. 2016 Jul;123(7):1581-7. doi: 10.1016/j.ophtha.2016.03.038. Epub 2016 May 24.
Derived from this study: PubMed 26992841Pieramici DJ, Wang PW, Ding B, Gune S. Visual and Anatomic Outcomes in Patients with Diabetic Macular Edema with Limited Initial Anatomic Response to Ranibizumab in RIDE and RISE. Ophthalmology. 2016 Jun;123(6):1345-50. doi: 10.1016/j.ophtha.2016.02.007. Epub 2016 Mar 15.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jason Ehrlich, M.D., Ph.D. study director

Genentech, Inc.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ranibizumab in people with Diabetes Mellitus and Macular Edema, run by Genentech, Inc..

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 8 inclusion and 27 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 17 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 17 Jan 2013). 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 Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Month 24 (time frame: Baseline to Month 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 NCT00473330, which also lists 19 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 17 Apr 2017.