Safety, Efficacy and Cost-efficacy of Ranibizumab (Monotherapy or Combination With Laser) in the Treatment of Diabetic Macular Edema (DME)

Diabetic Macular Edema Clinical Trial

— RESPOND  

Official title:

A Canadian 12-month, Prospective, Randomized, Open-label, Multicenter, Laser-controlled Phase IIIb Study Assessing the Efficacy, Safety and Cost-efficacy of Ranibizumab as Combination and Monotherapy in Patients With Visual Impairment Due to Diabetic Macular Edema.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01135914
• Other study ID #: CRFB002DCA05
• Status: Completed
• Phase: Phase 3
• First received: May 31, 2010
• Last updated: October 22, 2014
• Start date: July 2010
• Est. completion date: March 2013

Study information

• Verified date: October 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

To evaluate, specifically within the Canadian medical environment, the efficacy, safety and cost-efficacy of ranibizumab administered either as combination therapy (ranibizumab plus laser photocoagulation), or as monotherapy in comparison with the current standard of care (laser photocoagulation monotherapy), in patients with visual impairment due to DME.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 241
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Stable Type 1 or Type 2 diabetes mellitus

• Visual impairment due to focal or diffuse DME in at least one eye

Exclusion Criteria:

• Active conditions in the study eye that could prevent the improvement of visual acuity on study treatment

• Active eye infection or inflammation

• History of stroke, renal failure or uncontrolled hypertension

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Edema
• Macular Edema

Intervention

Drug:
• ranibizumab
Ranibizumab 0.5 mg fixed loading dose via intravitreal injection, given once per month for 3 consecutive months (Day 1, Month 1 and Month 2). This treatment could be reapllied, depending on symptoms.

Procedure:
• Laser
Laser photocoagulation treatment was administered on Day 1. Subsequent laser treatments could be administered if needed, in accordance with Early Treatment Diabetic Retinopathy Study (ETDRS) guidelines.

Locations

Country	Name	City	State
Canada	Calgary Retina Consultants	Calgary	Alberta
Canada	Clinique ChirurgiVision	Drummondville	Quebec
Canada	Victoria General Hospital, Department of Ophthalmology	Halifax	Nova Scotia
Canada	Ivey Eye Institute	London	Ontario
Canada	Canadian Centre for Advanced Eye Therapeutics	Mississauga	Ontario
Canada	Hôpital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Hôpital Notre Dame (CHUM)	Montreal	Quebec
Canada	Royal Victoria Hospital	Montreal	Quebec
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	Institut de l'oeil des Laurentides	Quebec
Canada	Centre Oculaire de Québec	Québec	Quebec
Canada	Saskatoon City Hospital / Spadina Clinic	Saskatoon	Saskatchewan
Canada	Dr.Michel Giunta Clinique Médicale	Sherbrooke	Quebec
Canada	Memorial University Health Sciences Centre / Bense Eye Centre	St-John's	Newfoundland and Labrador
Canada	Memorial University Health Sciences Centre / Newfoundland Drive Medical Clinic	St-John's
Canada	St-Michael's Hospital - Dept of Ophthalmology	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Toronto Western Hospital	Toronto	Ontario
Canada	UBC - Eye Care Center	Vancouver	British Columbia
Canada	Retina Consultants of Victoria	Victoria	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in Best Corrected Visual Acuity- (BCVA) at Month 12	Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of BCVA (EDTRS) is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement.	Baseline and 12 months	No
Secondary	Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Months 3,6 and 9	Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of BCVA (EDTRS)is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement.	Baseline, 3, 6 and 9 months	No
Secondary	Change From Baseline in Central Retinal Thickness (CRT) at Months 3,6,9 and 12	OCT is a diagnostic imaging technique using low-coherence interferometry to produce cross-sectional tomograms of the posterior segment eye structures. OCT was performed prior to study treatment to assess CRT, presence of fluid in the macula (intra-retinal cyst or fluid) and evaluation of image to monitor disease progression/treatment effect and to determine the need to stop/re-initiate ranibizumab treatment	Baseline, 3, 6, 9 and 12 months	No
Secondary	Percentage of Patients Achieving a Gain of 15-letters or More (3-lines) in BCVA From Baseline	Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of BCVA (EDTRS) is 0 to 100 letters. A higher percent of patients achieving a gain of =15 letters BCVA indicates a better response.	Baseline, 3, 6, 9 and 12 months	No
Secondary	Percentage of Patients Achieving Gain of Letters From Baseline in BCVA	Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of BCVA (EDTRS) is 0 to 100 letters. A gain of 5,10,15 or more BCVA letters from baseline indicates improvement.	12 months	No
Secondary	National Eye Institute Visual Functioning Questionnaire - 25 (VFQ-25) Composite Score at Month 12	The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) was used to measure the influence of visual disability and visual symptoms on general health domains. The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. For each question, the patient was asked to rate their condition on a scale of 1-5 or 1-6, where a low number reflects a better outcome. A composite score for a patient is calculated by aggregating and averaging the scores from the 11 sub-scales (excluding general health sub-scale), and an algorithm is apply to give equal weight to each sub-scale. Sub-scales and composite scores are calculated by converting the response from questionnaires into a 0-100 scale, with 0 as the worst possible outcome and 100 as the best. Missing data was not imputed	12 month	No
Secondary	EuroQoL (EQ-5D) Utility Score at Month 12	The Euro Quality of Life Questionnaire (EQ-5D) standardized instrument was utilized to measure health outcomes related to 5 dimensions, namely: mobility, self-care, usual activities, pain-discomfort, and anxiety/depression. The possible range for each dimension was 1 to 3, where 1="no problems", 2="some problems" and 3="extreme problems". Missing values were not imputed. Using the scoring algorithm derived from the Canadian value sets (Bansback et al., 2012), a utility score for a patient was calculated based on the EQ-5D responses for a given time-point at which the questionnaire was presented to the patient. This mean EQ-5D utility score ranged between 0 (worst health) to 1 (perfect health).	12 month	No
Secondary	Time Trade-Off Questionnaire - 25 (TTO) Composite Score at Month 12	(TTO) questionnaire was used to help determine the patients' health utility. Reported health utility represents the patients' quality of life at the current health state, and is a cardinal value that ranges from 0 (worst possible health or death) to 1 (best possible health). In this questionnaire, patients were first asked to estimate their remaining life expectancy. Second, the patients were presented with a hypothetical situation where a technology existed that could permanently return their vision to normal. This technology would always work, but would decrease their length of survival. Patients were then asked how much of their remaining life expectancy, if any, they would be willing to trade in return for use of the technology and thus for normal vision. The principle of this measure is that if patients were content with their current vision status (i.e., have a utility value of 1.0), they would not want to trade any of their remaining life years to improve their vision.	12 month	No