Phase 2 N=56 Randomized Triple-blind Treatment

Ranibizumab and Bevacizumab for Diabetic Macular Edema

Diabetic Macular Edema

Bottom Line

View on ClinicalTrials.gov: NCT01610557 ↗

Enrolled (actual)

Serious AEs

6.4%

Results posted

Apr 2016

Primary outcome: Primary: Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) From Baseline to 36 Weeks (Crossover Phase of the Study) — 5.3; 6.6 ETDRS letters — p=0.039

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Ranibizumab (Drug); Bevacizumab (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Eye Institute (NEI)
Primary completion: Feb 2015

Outcome Measures

Outcome	Result	p-value
PRIMARY Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) From Baseline to 36 Weeks (Crossover Phase of the Study)	5.3; 6.6	0.039 sig
SECONDARY Change in Central Retinal Thickness Assessed by Optical Coherence Tomography (OCT) Central Subfield Mean Thickness (CSMT) From Baseline to 36 Weeks (Crossover Phase of the Study)	-89; -137	<0.001 sig

Summary

Background: * Diabetic macular edema is a common eye complication of diabetes. It causes the blood vessels in the retina at the back of the eye to leak, causing swelling. The macula is the center part of the retina that is important for seeing fine details and for tasks such as reading, driving, or sewing. Swelling of the macula leads to vision loss and possible blindness. Inflammation may play a role in diabetic macular edema. It is also possible that there is a problem with the blood vessels and the blood supply to cells of the retina. * A chemical in the body called vascular endothelial growth factor (VEGF) is important in the formation of blood vessels in the body. Lowering VEGF levels may help treat diabetic macular edema by reducing abnormal leaking blood vessels in the eye. Drugs that can lower or block VEGF include ranibizumab and bevacizumab. Both drugs have been shown to help treat diabetic macular edema. Researchers want to see if one of the drugs works better than the other. Objective: To compare the effectiveness of ranibizumab and bevacizumab injections for diabetic macular edema. Eligibility: Individuals at least 18 years of age who have diabetic macular edema in at least one eye. Design: * Participants will be screened with a physical exam and medical history. A full eye exam will be performed. Blood and urine samples will be collected. * One eye will be selected as the study eye to receive treatment. If both eyes are affected, both eyes may be enrolled in the study and receive different drug treatments. * The main part of the study will last for 9 months. At each study visit, participants will have physical exams and eye exams. They will answer questions about their health and any side effects from the drugs. * Participants will be assigned to one of four groups. Two groups will have two series of ranibizumab and one series of bevacizumab shots. The other two groups will have two series of bevacizumab and one series of ranibizumab shots. A series is three eye injections of the same drug every 4 weeks. The injections will be given at these study visits. The series order will vary for the different groups. * After 9 months, participants will continue to have additional study visits. If the treatment seems to be successful, the study doctor may increase the time between visits. Study injections may be given as needed every 4 weeks for up to 3 years. * Participants may have laser treatments in a study eye if needed. After being in the study for 1 year, they may also have steroid injections or other treatments as directed for the macular edema.

Eligibility Criteria

INCLUSION CRITERIA

To be eligible, the following inclusion criteria must be met, where applicable.

Participant is 18 years of age or older.
Participant has a diagnosis of diabetic mellitus (type 1 or type 2). Any one of the following will be considered to be sufficient evidence that diabetes is present:
Current regular use of insulin for the treatment of diabetes;
Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes;
Documented diabetes by American Diabetes Association (ADA) and/or World Health Organization (WHO) criteria.
Participant must understand and sign the protocol's informed consent document.
Female participants of childbearing potential must not be pregnant or breast-feeding and must have a negative pregnancy test at screening and must agree to pregnancy testing throughout the study.
Female participants of childbearing potential and male participants able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two acceptable methods of contraception throughout the course of the study and for four weeks after their last injection. Acceptable methods of contraception include:
Hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring),
Intrauterine device,
Barrier methods (i.e., diaphragm, condom) with spermicide, or
Tubal ligation.
Participant has at least one eye that meets the study eye eligibility criteria.

EXCLUSION CRITERIA

A participant is not eligible if any of the following exclusion criteria are present.

Participant is in another investigational study and actively receiving investigational product for DME.
Participant has a known hypersensitivity to sodium fluorescein dye.
Participant has a condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control).
Participant has a history of chronic renal failure requiring dialysis or kidney transplant.
Participant has a history of liver failure.
Participant has a known hypersensitivity to bevacizumab, ranibizumab or any of their components.
Participant has a blood pressure of > 180/110 (systolic above 180 OR diastolic above 110).

--If blood pressure is brought below 180/110 by anti-hypertensive treatment, a patient can become eligible.

Participant has a history of treatment with oral steroids (greater than or equal to 10 mg of prednisone daily or equivalent) within three months prior to enrollment. Non-ocular depot and inhaled steroid treatments will not exclude a participant.
Participant has a history of treatment with systemic anti-VEGF agents within four weeks prior to enrollment.

STUDY EYE ELIGIBILITY CRITERIA:

The participant must have at least one eye meeting all inclusion criteria and none of the exclusion criteria listed below. Participants for whom both eyes meet all of the inclusion criteria and none of the exclusion criteria listed below may have both eyes enrolled in the study if they and the investigator so choose. If both eyes meet all of the inclusion criteria and none of the exclusion criteria listed below, and if the participant and the investigator decide that only one eye should be enrolled in the study, the study eye will be selected by the investigator in consultation with the participant.

STUDY EYE INCLUSION CRITERIA:

Eye has a BCVA ETDRS score between 20/32 and 20/400.
Eye has definite retinal thickening or cystic changes due to DME based on clinical exam involving the center of the macula that is not refractory to further therapy as based on the investigator's clinical judgment.
Eye has retinal thickness in the central subfield on baseline OCT measurement greater than or equal to 330 microns, as measured by Cirrus OCT.
Eye has clear ocular media and adequate pupillary dilation sufficien

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Data sourced from ClinicalTrials.gov (NCT01610557). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.