Ranibizumab and Bevacizumab for Diabetic Macular Edema
Verified September 2013 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
First received: May 31, 2012
Last updated: August 15, 2014
Last verified: September 2013
- 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 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.
- To compare the effectiveness of ranibizumab and bevacizumab injections for diabetic macular edema.
- Individuals at least 18 years of age who have diabetic macular edema in at least one eye.
- 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.
Diabetic Macular Edema
Drug: Ranibizumab and Bevacizumab
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Primary Purpose: Treatment
||A Phase II Randomized Study to Compare Anti-VEGF Agents in the Treatment of Diabetic Macular Edema (CADME)
Primary Outcome Measures:
- The primary outcome measure is the mean change in best-corrected visual acuity (BCVA).
Secondary Outcome Measures:
- Retinal thickness on Optical Coherence Tomography
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||August 2014 (Final data collection date for primary outcome measure)
Drug: Ranibizumab and Bevacizumab
Eyes are randomly assigned to receive a set sequence of monthly eye injections; all eyes receive ranibizumab at some time points and bevacizumab at others during the cross-over study.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
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 ADA and/or WHO criteria.
- Participant must understand and sign the protocol s informed consent document.
- Female participants of childbearing potential (see Appendix 1 for definition) 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 (see Appendix 1) 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 criteria listed in Section 3.2.
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 sufficient for adequate fundus photographs.
STUDY EYE EXCLUSION CRITERIA:
Eye has macular edema considered to be due to a cause other than diabetes.
An eye is not eligible if:
- The macular edema is considered to be related to cataract extraction; or
- Clinical examination and/or OCT suggest that vitreoretinal interface disease (e.g., a taut posterior hyaloid or epiretinal membrane) is the primary cause of the macular edema.
- Eye has an ocular condition present such that, in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (e.g., foveal atrophy, pigmentary changes, dense subfoveal hard exudates, non-retinal condition).
- Eye has an ocular condition present (other than DR) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome, etc.).
- Eye has a history of panretinal scatter photocoagulation (PRP) within three months prior to enrollment.
- Eye has a history of prior pars plana vitrectomy prior to enrollment.
- Eye has a history of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within three months prior to enrollment.
- Eye has a history of Yttrium-Aluminum-Garnet (YAG) capsulotomy performed within two months prior to enrollment.
- Eye had laser photocoagulation treatment, or received intravitreal or periocular steroids within three months prior to enrollment.
- Eye has a history of intravitreal anti-VEGF agents within eight weeks prior to enrollment.
- Eye has had greater than four intravitreal anti-VEGF injections within one year prior to enrollment.
- Eye has high-risk proliferative DR requiring laser photocoagulation treatment.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01610557
|National Institutes of Health Clinical Center, 9000 Rockville Pike
|Bethesda, Maryland, United States, 20892 |
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org |
|Bristol Eye Hospital
|Bristol, United Kingdom |
||Henry E Wiley, M.D.
||National Eye Institute (NEI)
||National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
History of Changes
|Other Study ID Numbers:
|Study First Received:
||May 31, 2012
||August 15, 2014
||United States: Federal Government
Keywords provided by National Institutes of Health Clinical Center (CC):
Diabetic Macular Edema
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on August 19, 2014
Signs and Symptoms
Angiogenesis Modulating Agents
Physiological Effects of Drugs