Proliferative Diabetic RetinopathyPhase 4NCT02005432
PASCAL Laser Versus ETDRS Laser Associated With Intravitreal Ranibizumab (IVR) Versus Only IVR for Proliferative Diabetic Retinopathy
A Phase 4 study testing Intravitreal Ranibizumabe, panfotocoagulation (PASCAL) and panfotocoagulation (PRP) single shoot (ETDRS) in people with Proliferative Diabetic Retinopathy, run by University of Sao Paulo at 1 site in Brazil.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Proliferative Diabetic Retinopathy
- What is being tested?
- Intravitreal Ranibizumabe, panfotocoagulation (PASCAL) and panfotocoagulation (PRP) single shoot (ETDRS)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteBrazil
- Study dates
- Feb 2012to Nov 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diabetic patients older than 18 years
- 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
- Giving written informed consent.
Who cannot join
- 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
- Presence of ring-shaped retinal neovascularization extending along both temporal arcades and the optic disc
- Any abnormality of the vitreoretinal interface in the macular region for which the investigator would consider vitrectomy via pars plana to be necessary
- Intravitreous injection of corticosteroids or of other antiangiogenic drugs 6 months before the evaluation for entry into the study
- Inability to fixate and to conclude the automated static perimetry exam
- Cataract surgery within the last three months
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- Posterior vitrectomy with scleral introflexion at any time
- Acute ocular infection
- Allerghy to fluorescein
- Medical or psychological conditions that would prevent the patient from giving informed consent and concluding the study
- Significant uncontrolled diseases which, in the opinion of the investigator, would exclude the patient from the study
- Renal failure requiring dialysis or renal transplant or renal insufficiency with creatinine levels >2.0 mg/dl
- Untreated diabetes mellitus
- Severe (blood pressure systolic > 160 mmHg or diastolic > 100 mmHg) AND untreated hypertension
- Inability to comply with study or follow-up procedures.
- Impaired or limited legal capacity
- Participation in another clinical study in the last 30 days.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Retina and Vitreous service of the University Hospital, Faculty of Medicine of Ribeirão Preto-USP (HCFMRP)
Ribeirão Preto, São Paulo
About this study
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.
Objectives:
Primary objective:
Read more
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).
Read the detailed 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.
- Conditions
- Proliferative Diabetic Retinopathy
- Being tested
- Intravitreal Ranibizumabe, panfotocoagulation (PASCAL), panfotocoagulation (PRP) single shoot (ETDRS)
- Keywords
- Diabetis, Retinal Neovascularization, laser treatment
- Medical subject headings
- Retinal Neovascularization
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravitreal RanibizumabeDrug
Intravitreal injection 0,05ml Ranibizumabe
panfotocoagulation (PASCAL)Drug
panfotocoagulation (PRP) single shoot (ETDRS)Drug
| Study group | Role | What they receive |
|---|---|---|
| SS-PRP arm | Active comparator | panfotocoagulation (PRP) single shoot (ETDRS) + 0,05ml intravitreal injection anti-VEGF (ranibizumabe) Receives: Drug: Intravitreal Ranibizumabe; Drug: panfotocoagulation (PRP) single shoot (ETDRS) |
| MS-PRP arm | Experimental | Multiple shoot panfotocoagulation (PASCAL) plus IVR Receives: Drug: Intravitreal Ranibizumabe; Drug: panfotocoagulation (PASCAL) |
| IVR arm | Other | only IVR (intravitreal Ranibizumabe) Receives: Drug: Intravitreal Ranibizumabe |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: from baseline to week 48.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2013 (estimated)
- Study startFeb 2012
- Primary completionNov 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Proliferative Diabetic RetinopathyStudies of the same condition, open and under way.
- More trials run by University of Sao PauloThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rafael de Montier P. Barroso, MD, University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02005432
- Sponsor's protocol ID
- IRALA
- Status last verified
- Dec 2013
- First submitted
- 3 Dec 2013
- Last updated
- 9 Dec 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Barroso RMP, Messias K, Garcia DM, Cardillo JA, Scott IU, Messias A, Jorge R. ETDRS panretinal photocoagulation combined with intravitreal ranibizumab versus PASCAL panretinal photocoagulation with intravitreal ranibizumab versus intravitreal ranibizumab alone for the treatment of proliferative diabetic retinopathy. Arq Bras Oftalmol. 2020 Nov-Dec;83(6):526-534. doi: 10.5935/0004-2749.20200096.
PubMed 33470281
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02005432
- Acronym / sponsor ID
- IRALA
- Conditions
- Proliferative Diabetic Retinopathy
- Keywords
- Diabetis, Retinal Neovascularization, laser treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- Nov 2014 (estimated)
- First posted
- 9 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SS-PRP arm | Active comparator | Drug: Intravitreal Ranibizumabe, Drug: panfotocoagulation (PRP) single shoot (ETDRS)panfotocoagulation (PRP) single shoot (ETDRS) + 0,05ml intravitreal injection anti-VEGF (ranibizumabe) |
| MS-PRP arm | Experimental | Drug: Intravitreal Ranibizumabe, Drug: panfotocoagulation (PASCAL)Multiple shoot panfotocoagulation (PASCAL) plus IVR |
| IVR arm | Other | Drug: Intravitreal Ranibizumabeonly IVR (intravitreal Ranibizumabe) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diabetic patients older than 18 years
- 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
- Giving written informed consent.
Key exclusion criteria (17 listed)
- 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
- Presence of ring-shaped retinal neovascularization extending along both temporal arcades and the optic disc
- Any abnormality of the vitreoretinal interface in the macular region for which the investigator would consider vitrectomy via pars plana to be necessary
- Intravitreous injection of corticosteroids or of other antiangiogenic drugs 6 months before the evaluation for entry into the study
- Inability to fixate and to conclude the automated static perimetry exam
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravitreal RanibizumabeIntravitreal injection 0,05ml Ranibizumabe | Drug | IVR arm, MS-PRP arm, SS-PRP arm |
| panfotocoagulation (PASCAL) | Drug | MS-PRP arm |
| panfotocoagulation (PRP) single shoot (ETDRS) | Drug | SS-PRP arm |
Primary outcome
fluorescein angiography leakage area
Time frame: from baseline to week 48.
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2013.
- Derived from this study: PubMed 33470281Barroso RMP, Messias K, Garcia DM, Cardillo JA, Scott IU, Messias A, Jorge R. ETDRS panretinal photocoagulation combined with intravitreal ranibizumab versus PASCAL panretinal photocoagulation with intravitreal ranibizumab versus intravitreal ranibizumab alone for the treatment of proliferative diabetic retinopathy. Arq Bras Oftalmol. 2020 Nov-Dec;83(6):526-534. doi: 10.5935/0004-2749.20200096.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Intravitreal Ranibizumabe, panfotocoagulation (PASCAL) and panfotocoagulation (PRP) single shoot (ETDRS) in people with Proliferative Diabetic Retinopathy, run by University of Sao Paulo at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
fluorescein angiography leakage area (time frame: from baseline to week 48.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02005432, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2013.