Multicenter 12 Months Clinical Study to Evaluate Efficacy and Safety of Ranibizumab Alone or in Combination With Laser Photocoagulation vs. Laser Photocoagulation Alone in Proliferative Diabetic Retinopathy (PRIDE)

Phase 2

Completed

• Conditions: Proliferative Diabetic Retinopathy (PDR)
• Interventions: Drug: Ranibizumab 0.5 mg; Procedure: Panretinal laser photocoagulation

• Registration Number: NCT01594281
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

The purpose of this study was to assess the efficacy and safety of the anti-Vascular Endothelial Growth Factor (VEGF) agent ranibizumab (0.5 mg) with or without Panretinal laser photocoagulation (PRP) compared to PRP alone in patients with Proliferative Diabetic Retinopathy (PDR).

Detailed Description

A 12-month core phase was followed by a 12-month observational follow-up phase (physician's routine), for a planned individual study duration of 24-25 months. A separate informed consent was signed for the 12-month observational follow-up phase. This study was conducted in Germany.

Study Timeline

• Study First Submitted: 2012-05-03
• Study First Submitted QC: 2012-05-07
• Study First Posted: 2012-05-09
• Study Start: 2012-12-11
• Primary Completion: 2016-11-30
• Study Completion: 2017-12-05
• Status Verified: 2018-11
• Results First Submitted: 2018-11-19
• Results First Submitted QC: 2018-11-20
• Last Update Submitted: 2018-11-20
• Results First Posted: 2019-03-15
• Last Update Posted: 2019-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 107

Inclusion Criteria

• Proliferative Diabetic Retinopathy
• Best Corrected Visual Acuity (BCVA) in study eye of at least 20 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/400)
• Type 1 or type 2 diabetes under medical surveillance / with stabilized treatment

Exclusion Criteria

• Proliferative vitreoretinopathy in study eye
• Clinically significant macular edema (CSME) in the study eye
• Clinically non significant macular edema (CNSME) that is likely to develop to CSME in the study eye
• Uncontrolled glaucoma in either eye
• Other protocol-specified conditions

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ranibizumab mono	Ranibizumab 0.5 mg	Interventional Core Phase: One intravitreal injection of ranibizumab 0.5 mg to the study eye monthly until stability regarding morphological parameters is confirmed (ie, no further improvement of morphology or no worsening of morphology for 3 consecutive months)
Ranibizumab+PRP	Panretinal laser photocoagulation	Interventional Core Phase: Ranibizumab 0.5 mg as described for the ranibizumab mono arm and PRP treatment as described for the PRP mono arm until stability regarding morphological parameters is confirmed
Ranibizumab+PRP	Ranibizumab 0.5 mg	Interventional Core Phase: Ranibizumab 0.5 mg as described for the ranibizumab mono arm and PRP treatment as described for the PRP mono arm until stability regarding morphological parameters is confirmed
PRP mono	Panretinal laser photocoagulation	Interventional Core Phase: Panretinal laser photocoagulation (PRP) treatment administered to the study eye in accordance with the modified diabetic retinopathy study (DRS) guidelines for panretinal laser photocoagulation procedures

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Area of Neovascularizations (NVs) at End of Core Study (EOCS)	Baseline, EOCS	The area of neovascularizations (NV) was assessed by a central reading center via fluorescein angiography (FA) images. The area of NV was calculated as the sum of area of neovascularization of the disc (NVD) and neovascularization elsewhere (NVE) and was recorded in square millimeters. A higher positive change value may indicate a greater formation of new, abnormal blood vessels and thus disease progression. One eye (study eye) contributed to the analysis.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Area of Neovascularizations (NVs) at Month 3	Baseline, Month 3	The area of neovascularizations (NV) was assessed by a central reading center via fluorescein angiography (FA) images. The area of NV was calculated as the sum of area of neovascularization of the disc (NVD) and neovascularization elsewhere (NVE) and was recorded in square millimeters. A higher positive change value may indicate a greater formation of new, abnormal blood vessels and thus disease progression. One eye (study eye) contributed to the analysis.
Number of Patients With Change From Baseline in ETDRS Severity Grade of Diabetic Retinopathy (DR) at EOCS	Baseline, EOCS	The severity level of diabetic retinopathy was determined using the ETDRS severity scale. However, in contrast to the original ETDRS severity scale, wide field fluorescein angiography images were used in addition to color fundus photography for identification of NVs and prior PRP treatment was not considered for determining the severity level. Eyes could be graded in the following classes: "DR absent" (10), "questionable DR" (14,15), "NPDR" (20-53), "mild PDR" (60-61), "moderate PDR" (65), "high risk PDR" (71-75), "advanced PDR" (81-85) and "cannot grade" (90). One eye (study eye) contributed to the analysis. No statistical analysis was conducted for ≥ 1 class deterioration or ≥ 2 class deterioration from Baseline at EOCS because ratios could not be calculated in case of zero frequencies in at least one of the three treatment groups.
Change From Baseline in Central Subfield Thickness at EOCS	Baseline, EOCS	Central subfield retinal thickness was assessed by a central reading center using Optical Coherence Tomography images. A positive change value may indicate disease progression. One eye (study eye) contributed to the analysis.
Best Corrected Visual Acuity (BCVA) (ETDRS Letters) at EOCS	EOCS	BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at a testing distance of 4 meters. A higher number of ETDRS letters may indicate better visual acuity. One eye (study eye) contributed to the analysis.
Number of Ranibizumab Injections Until EOCS	Baseline to EOCS	The total number of ranibizumab injections until EOCS was calculated. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.
Number of PRP Laser Spots Until EOCS	Baseline to EOCS	The total number of PRP laser spots from baseline until EOCS was calculated. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.
Percentage of Patients With Change From Baseline in BCVA (ETDRS Letters) at EOCS	Baseline, EOCS	BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at a testing distance of 4 meters. No clinically relevant change was defined as \<5 letters gain or loss. A higher positive change value may indicate a greater improvement in visual acuity. One eye (study eye) contributed to the analysis.
Change From Baseline in Foveal Center Point Retinal Thickness at EOCS	Baseline, EOCS	Foveal center point retinal thickness was assessed by a central reading center using Optical Coherence Tomography images. A positive change value may indicate disease progression. One eye (study eye) contributed to the analysis.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇩🇪 Ulm, Germany