PASCAL Laser Versus ETDRS Laser Associated With Intravitreal Ranibizumab (IVR) Versus Only IVR for Proliferative Diabetic Retinopathy

Proliferative Diabetic Retinopathy Clinical Trial

Official title:

Three Arm, Prospective, Single-blind, Randomized Study Comparing Ranibizumab Plus Green Diode Laser Versus Ranibizumab Plus Pattern Scan Laser (Pascal) Versus Ranibizumab (Monotherapy) for Proliferative Diabetic Retinopathy.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02005432
• Other study ID #: IRALA
• Status: Active, not recruiting
• Phase: Phase 4
• First received: December 3, 2013
• Last updated: December 6, 2013
• Start date: February 2012

Study information

• Verified date: December 2013
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Objectives:

Primary objective:

To evaluate the effects on retinal morphophysiology of full scatter single target panretinal photocoagulation (PRP) versus full scatter multiple target panretinal photocoagulation (both combined with intravitreous injections of ranibizumab) versus intravitreous ranibizumab (IVR) alone in patients with proliferative diabetic retinopathy (PDR).

Primary outcome:

The primary endpoint for this study is the mean change in the total area of active retinal neovessels, as measured by fluorescein angiography leakage area, in mm2, from baseline to week 48.

Secondary objectives:

• To assess the mean changes in best corrected visual acuity (BCVA), the mean changes in central subfield foveal thickness (CSFT), the mean changes in wave B amplitude and oscillatory potentials on a full-field electroretinogram (ERG), and the mean changes on the peripheral visual field by static perimetry (30:2 strategy), from baseline to week 48.

• To assess the incidence of adverse events during the study.

Strategic goal:

In the era of anti-VEGF treatment for retinal neovascularization 1, 2, 3, 4 , it is time to determine what would be the best association of PRP + anti-VEGF for proliferative diabetic retinopathy (PDR), or still, if just intravitreal anti-VEGF treatment would be even better regarding morphologic (new vessels area and CSFT) and functional parameters (BCVA, ERG response and visual field).

Description:

Photocoagulation (thermal laser) was the first modality to be described for the treatment of PDR. Different types of laser such as xenon, krypton, argon, red diode and green diode can be used for this treatment. The Early Treatment Diabetic Retinopathy Study (ETDRS) showed the benefit of early treatment of PDR and of macular edema with laser photocoagulation.

However, several studies have reported loss of visual field after laser photocoagulation of the bilateral full-scatter type (PRP) due to the expansion of the thermal injury, possibly even compromising the ability to drive automotive vehicles according to the standards of the transit authorities of some countries. Thus, this implies a greater impact on the quality of life of the patient, especially if he is a young diabetic.6

The objective of new laser photocoagulation technologies is to provide a treatment that will permit the development of a regenerative response of photoreceptors and of the retinal pigment epithelium (RPE) with the minimum loss of photoreceptors and the minimum cicatricial expansion of the thermal injury on the targeted RPE.7

The PASCAL photocoagulator (OptiMedica, Santa Clara, California) (a standard scanning laser) was introduced in 2005 for retinal photocoagulation. The device functions as if it partially automated the procedure by means of a shorter laser pulse (short pulse strategy) combined with multiple simultaneous firings in a pattern, performing the procedure within a shorter period of time and with less damage to the outer retina or the RPE, in addition to providing better patient comfort.8

Regarding combined therapy, the combination of intravitreous injection of ranibizumab with PRP (ETDRS) proved to be more promising in terms of improved visual acuity, stability of macular thickness and a greater regression rate of neovessel areas than the use of PRP alone (ETDRS) in patients with high risk PDR.1

Thus, in the present study we would like to determine which would be the best therapeutic combination of laser and an anti-VEGF drug for our patients, or whether treatment with an anti-VEGF drug alone would be better in terms of the anatomical and functional parameters proposed.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 31
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Diabetic patients older than 18 years

2. Presence of PDR (presence of retinal neovascularization, defined as active neovessels (fine retinal vessels with saccular dilatations or extremities covered with blood or associated with recurrent vitreous hemorrhage) with visual acuity better than 20/800 and with no previous laser treatment

3. Giving written informed consent.

Exclusion Criteria:

1. Presence of advanced PDR, i.e.: vitreous hemorrhage that would prevent documentation of the eye fundus or adequate retinal photocoagulation, or presence of traction retinal detachment

2. Presence of ring-shaped retinal neovascularization extending along both temporal arcades and the optic disc

3. Any abnormality of the vitreoretinal interface in the macular region for which the investigator would consider vitrectomy via pars plana to be necessary

4. Intravitreous injection of corticosteroids or of other antiangiogenic drugs 6 months before the evaluation for entry into the study

5. Inability to fixate and to conclude the automated static perimetry exam

6. Cataract surgery within the last three months

7. Posterior vitrectomy with scleral introflexion at any time

8. Acute ocular infection

9. Allerghy to fluorescein

10. Medical or psychological conditions that would prevent the patient from giving informed consent and concluding the study

11. Significant uncontrolled diseases which, in the opinion of the investigator, would exclude the patient from the study

12. Renal failure requiring dialysis or renal transplant or renal insufficiency with creatinine levels >2.0 mg/dl

13. Untreated diabetes mellitus

14. Severe (blood pressure systolic > 160 mmHg or diastolic > 100 mmHg) AND untreated hypertension

15. Inability to comply with study or follow-up procedures.

16. Impaired or limited legal capacity

17. Participation in another clinical study in the last 30 days.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Proliferative Diabetic Retinopathy
• Retinal Diseases

Intervention

Drug:
• Intravitreal Ranibizumabe
Intravitreal injection 0,05ml Ranibizumabe
• panfotocoagulation (PASCAL)

• panfotocoagulation (PRP) single shoot (ETDRS)

Locations

Country	Name	City	State
Brazil	Retina and Vitreous service of the University Hospital, Faculty of Medicine of Ribeirão Preto-USP (HCFMRP)	Ribeirao Preto	Sao Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	fluorescein angiography leakage area	The primary endpoint for this study is the mean change in the total area of active retinal neovessels, as measured by fluorescein angiography leakage area, in mm2.	from baseline to week 48.	No