Treatment of Refractory Diabetic Macular Edema With Infliximab

This study has been terminated.
(The number of the anticipated participants was not achieved)
Sponsor:
Information provided by:
University of Athens
ClinicalTrials.gov Identifier:
NCT00505947
First received: July 23, 2007
Last updated: February 19, 2009
Last verified: February 2009
  Purpose

The purpose of this study is to determine if treatment with infliximab improves macular edema which is refractory to laser photocoagulation in patients with diabetes.


Condition Intervention Phase
Diabetic Macular Edema
Visual Acuity
Diabetic Retinopathy
Drug: infliximab
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Infliximab for Diabetic Macular Edema Refractory to Laser Photocoagulation: a Randomized, Double-Masked, Placebo-Controlled, Cross-Over, 32 Weeks Study

Resource links provided by NLM:


Further study details as provided by University of Athens:

Primary Outcome Measures:
  • improvement in best corrected visual acuity [ Time Frame: 32 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • anatomical improvement of diabetic macular edema and improvement in diabetic retinopathy [ Time Frame: 32 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 12
Study Start Date: July 2007
Study Completion Date: December 2008
Estimated Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A

Infliximab 5 mg/Kg body weight by intravenous infusion on visit 1 (week 0), visit 2 (week 2), visit 3 (week 6)and visit 5 (week 14).

Afterwards, after a washout period of 2 weeks, arm A will receive placebo at visits 6 (week 16), visit 7 (week 18), visit 8 (week 22)and visit 30 (week 30)

Drug: infliximab
infliximab 5 mg/Kg body weight by intravenous infusion
Other Name: Remicade
Drug: placebo
placebo 5 mg/Kg body weight by intravenous infusion
Other Name: placebo: a solution of similar appearance with infliximab
Placebo Comparator: B

Arm B will receive placebo at visit 1 (week 0), visit 2 (week 2), visit 3 (week 6)and visit 5 (week 14).

Afterwards, after a washout period of 2 weeks, group B will receive infliximab 5 mg/Kg body weight by intravenous infusion at visit 6 (week 16), visit 7 (week 18), visit 8 (week 22)and visit 30 (week 30)

Drug: infliximab
infliximab 5 mg/Kg body weight by intravenous infusion
Other Name: Remicade
Drug: placebo
placebo 5 mg/Kg body weight by intravenous infusion
Other Name: placebo: a solution of similar appearance with infliximab

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have the capacity to understand and sign an informed consent form.
  • Signed informed consent (must be obtained before any specific procedure is performed).
  • Presence of clinically significant macular edema, with visual acuity less than 0.4 corrected to EDRS scale, which is refractory to at least two sessions of laser photocoagulation, defined as: A) Thickening of the retina at or within 500 μm of the center of the macula. B) Hard exudates at or within 500 μm of the center of the macula, if associated with thickening of the adjacent retina. C) A zone or zones of retinal thickening 1 disc area or larger, any part of which is within 1 disc diameter of the center of the macula.
  • Male or female aged 18-80 years, inclusive.
  • Type 1 or type 2 diabetes of at least 1 year duration. Type 1 diabetes is defined clinically as a diagnosis made before the age of 36 years with a continuous need for insulin within a year of diagnosis. Type 2 diabetes is defined clinically as a diagnosis made at age of 36 or above without a need for continuous insulin therapy within a year of diagnosis.
  • Postmenopausal women (no menstrual cycle for a period of a minimum of 1 year) or surgically sterilized and have a negative serum pregnancy test on entry in the study. Men must agree to use adequate birth control during the study for 6 months after the infusion of the study agent.
  • Men and women of childbearing potential must use adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) for the duration of the study and should continue such precautions for 6 months after receiving the last infusion.
  • Stable diabetic therapy within the last 6 months, i.e. absence of major change in glycemic control (e.g. 2% change in HbA1c) or change in daily number of insulin injections.
  • HbA1c 6.2-10%.
  • The screening laboratory test must meet the following criteria: white blood cell count >5x10/L; absolute neutrophil count >1x10/L; platelet count >50x10/L; haemoglobin >100 g/L; serum creatinine <2 mg/dl; aspartate aminotransferase < 3 times the upper normal limit; alanine aminotransferase <3 times the upper normal limit; alkaline phosphatase < 2 times the upper normal limit, γ-GT< 2 times the upper normal limit
  • Patients are considered eligible according to the following tuberculosis (TB) screening criteria: A)Have no history of latent or active TB prior to screening. B)Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination. C)Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study agent. D) Within 1 month prior to the first administration of study agent, either have a negative tuberculin skin test, as outlined in appendix B, or have a newly identified positive tuberculin skin test during screening in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study agent. E)Have a chest radiograph (both posterior-anterior and lateral views), taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current active TB or old inactive TB.

Exclusion Criteria:

  • Vitreoretinal traction.
  • Retinal detachment.
  • Proliferative diabetic retinopathy requiring immediate panretinal photocoagulation.
  • Any previous eye surgery in the last 6 months before the beginning of the study (intravitreal injections are not considered ocular surgery).
  • Macular Edema of ischaemic type.
  • Macular Edema caused by retinal conditions other than diabetes.
  • Cataract or media opacities of a degree which precludes accurate retinal photographs or OCT measurement.
  • Hard exudates under the fovea.
  • Uncontrolled hypertension (blood pressure above 180/110 mmHg).
  • Angle closure glaucoma which precludes pharmacological dilatation of the pupil.
  • Use in the previous 6 months of oral corticosteroids or in the previous month of anti-inflammatory medication.
  • Women who are pregnant, nursing, or planning pregnancy within 6 months after the last infusion) (this includes fathers who plan on fathering a child within 6 months after their last infusion).
  • Have had any previous treatment with monoclonal antibodies or antibody fragments.
  • History of receiving human/murine recombinant products or a known allergy to murine products. A known allergy to murine product is definitely an exclusion criterion.
  • Documentation of seropositivity for human immunodeficiency virus (HIV).
  • A positive test for hepatitis B surface antigen or hepatitis C virus (HCV).
  • Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of the results.
  • Have a known history of serious infections (e.g. hepatitis, pneumonia, or pyelonephritis) in the previous 3 months.
  • Have or have had an opportunistic infection (e.g. herpes zoster, cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than tuberculosis) within 6 months prior to screening.
  • Positive PPD test.
  • Have a chest radiograph at screening that shows evidence of malignancy, infection, or any abnormalities suggestive of TB.
  • Have a history of lymphoproliferative disease, including lymphoma or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location (e.g. nodes in the posterior triangle of the neck, infraclavicular, epitrocheal, or periaortic area), or splenomegaly.
  • Currently have a known malignancy or have a malignancy within the previous 5 years, with the exception of basal or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence.
  • Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological or cerebral disease.
  • Are unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access.
  • Use of any investigational drug within 6 months prior to screening.
  • Presence of transplanted solid organ (with the exception of corneal transplant > 3 months prior to screening).
  • Have a concomitant diagnosis or history of congestive heart failure.
  • Blood donation for the duration of the study
  • Have allergy or other contraindication to fluorescein
  Contacts and Locations
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: NCT00505947

Locations
Greece
University of Athens
Athens, Greece, 11527
Medical School, University of Athens
Athens, Greece, 11527
Sponsors and Collaborators
University of Athens
Investigators
Principal Investigator: Petros Sfikakis, MD University of Athens
  More Information

No publications provided by University of Athens

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Petros Sfikakis, University of Athens
ClinicalTrials.gov Identifier: NCT00505947     History of Changes
Other Study ID Numbers: C0168X97, EU-0129
Study First Received: July 23, 2007
Last Updated: February 19, 2009
Health Authority: Greece: National Organization of Medicines

Keywords provided by University of Athens:
macular edema
diabetes mellitus
visual loss
diabetic retinopathy
macula
maculopathy
infliximab

Additional relevant MeSH terms:
Diabetic Retinopathy
Edema
Macular Edema
Retinal Diseases
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Infliximab
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014