High Risk Proliferative Diabetic RetinopathyPhase 2NCT01281098
Prospective, Randomized, Open Label, Phase II Study to Assess Efficacy and Safety of Macugen® (Pegaptanib 0.3 mg Intravitreal Injections) Plus Panretinal Photocoagulation and PRP (Monotherapy) in the Treatment With High Risk PDR.
A Phase 2 study testing Panretinal Photocoagulation (PRP) and Intravitreous injection of pegaptanib in people with High Risk Proliferative Diabetic Retinopathy and Diabetes Mellitus Type I, run by Association for Innovation and Biomedical Research on Light and Image at 1 site in Portugal.
Trial summary
To evaluate the safety and determine the efficacy of PRP monotherapy or combination therapy (pegaptanib 0.3 mg plus PRP) in patients with Type I or Type II diabetes mellitus and with high risk proliferative diabetic retinopathy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High Risk Proliferative Diabetic Retinopathy, Diabetes Mellitus Type I, Diabetes Mellitus Type II
- What is being tested?
- Panretinal Photocoagulation (PRP) and Intravitreous injection of pegaptanib
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 sitePortugal
- Study dates
- Mar 2010to Feb 2013
- Phase
- Phase 2
- 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
- High-risk proliferative diabetic retinopathy (HR-PDR) eyes (as defined in section 2).
- BCVA at baseline > 20/320 (25 letters in the ETDRS Chart) in the study eye.
- Clear ocular media and adequate pupillary dilatation to permit good quality fundus photography.
- Intraocular pressure < 21 mmHg.
- Type I, or Type II diabetic subjects as defined by the WHO criteria of either gender, and aged ≥ 18 years.
- Women must be using effective contraception, be post-menopausal for at least 12 months prior to trial entry, or surgically sterile.
- Ability to provide written informed consent.
- Ability to return for all trial visits.
Who cannot join
- Eyes with prior scatter (panretinal).
- Focal/grid photocoagulation, within the previous 6 months.
- Fibrovascular proliferation with retinal traction.
- Other cause of retinal neovascularization (retinal vein occlusion, radiation retinopathy or others).
- Atrophy/scarring/fibrosis/ hard exudates involving the center of the macula.
- Subjects who have received YAG laser within the previous 6 months.
Show all 30Show fewer
- Peripheral retinal cryoablation, or laser retinopexy (for retinal tears only),
- Significant media opacities, which might interfere with visual acuity, assessment of toxicity or fundus photography.
- Subjects should not be entered if there is likelihood that they will require cataract surgery within the following 1 year.
- Any intraocular surgery within 6 months before trial enrolment.
- Previous vitrectomy.
- HbA1C level >11% or recent signs of uncontrolled diabetes.
- Any of the following underlying systemic diseases:
- History or evidence of severe cardiac disease, e.g. NYHA Functional Class III or IV, clinical or medical history of unstable angina, acute coronary syndrome, myocardial infarction, or revascularization procedure within 6 months prior to baseline, or ventricular tachyarrhythmia requiring treatment.
- History or evidence of clinically significant peripheral vascular disease such as intermittent claudication or prior amputation.
- Clinically significant impaired renal function (serum creatinine >2.5 mg/dL or s/p renal transplant or receiving dialysis).
- Clinically significant impaired hepatic function.
- Stroke (within 12 months of trial entry).
- Any major surgical procedure within one month before trial enrolment.
- Previous radiation to the head in the region of the study eye.
- Any prior treatment with an investigational agent for diabetic retinopathy or anti-VEGF therapy (including intravitreal, subconjunctival or subtenons corticosteroids) during the past 90 days for any other condition.
- Known serious allergies to fluorescein used in angiography, or to components of Macugen® formulation.
- Systolic BP > 170 (2 different readings) or diastolic BP > 100 (2 different readings).
- Acute ocular or periocular infection.
- Previous filtering surgery (e.g., trabeculectomy) or placement of a glaucoma drainage devise (e.g., tube-shunt surgery).
- Use of other investigational drugs at the time of enrollment.
- History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant UNLESS they are: women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner; women whose partners have been sterilized by vasectomy or other means using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices - IUDs). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) are not acceptable.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective, Randomized, Open Label, Phase II Study to Assess Efficacy and Safety of Macugen® (Pegaptanib 0.3 mg Intravitreal Injections) Plus Panretinal Photocoagulation (PRP) and PRP (Monotherapy) in the Treatment of Patients With High Risk Proliferative Diabetic Retinopathy (PDR).
To evaluate the safety and determine the efficacy of PRP monotherapy or combination therapy (pegaptanib 0.3 mg plus PRP) in patients with Type I or Type II diabetes mellitus and with high risk proliferative diabetic retinopathy.
Read the detailed description
Panretinal photocoagulation (PRP) can cause regression of retinal neovascularization and reduce the risk of severe vision loss in people with proliferative diabetic retinopathy (PDR). However, this destructive treatment may be associated with side effects (e.g. pain, transient blurring, loss of peripheral and/or night vision, increased risk of macular edema and central vision loss) and it is not always efficient in the regression of the neovascularization.
Vascular endothelial growth factor (VEGF) has been shown to play a role in retinal neovascularization and retinal vascular leakage related with PDR and diabetic macular edema.
Anti-VEGF treatments have been hypothesized as an adjunctive treatment for the management of retinal neovascularization and macular edema related with diabetic retinopathy (DR).
Anti-VEGF agents, such as Macugen®, combined with PRP are expected to control neovascularization without the need for photocoagulation of the posterior pole, around the macula, thus avoiding the major side effects of standard PRP (visual field loss).
A modification of panretinal photocoagulation (PRP) was recently proposed by Madeira et al., (2009) at the 2009 EURETINA Meeting. The described technique involves the progressive application of the DRS photocoagulation rings in a different sequence. First ring: corresponds to the DRS third ring, extruding from the ora serrata to the midperiphery. Second ring: corresponds to DRS second ring, extruding from the midperiphery towards the vortex veins. Third ring: corresponds to DRS first ring, and will only be performed if necessary. This technique resulted in less aggressive visual fields losses by achieving results with only most peripheral photocoagulation. The combination of intravitreal anti-VEGF treatment with pegaptanib, where a series of 3 injections are injected to reverse the neovascularization, while maintaining the macula dry will be completed by the more long term effect of the panretinal photocoagulation. This peripheral photocoagulation proposed is expected to eliminate the chronic VEGF stimulus by eliminating the chronic ischemic factor, while maintaining the visual fields useful for daily activities such as driving, etc.
- Conditions
- High Risk Proliferative Diabetic Retinopathy, Diabetes Mellitus Type I, Diabetes Mellitus Type II
- Being tested
- Panretinal Photocoagulation (PRP), Intravitreous injection of pegaptanib
- Keywords
- High Risk Proliferative Diabetic Retinopathy, Diabetes Mellitus Type I, Type II, Pegaptanib, Panretinal Photocoagulation
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Panretinal Photocoagulation (PRP)Procedure or surgery
Panretinal Photocoagulation (PRP)
Intravitreous injection of pegaptanibDrug
Intravitreous injection of pegaptanib
| Study group | Role | What they receive |
|---|---|---|
| Panretinal Photocoagulation (PRP) | Active comparator | Group 1: Panretinal photocoagulation treatment (PRP) at week-0 that can be repeated every 6 weeks. Receives: Procedure: Panretinal Photocoagulation (PRP) |
| Pegaptanib + Panretinal Photocoagulation (PRP) | Experimental | Group 2: Combination treatment of pegaptanib intravitreous injections at weeks 0, 6 and 12 that can be repeated every 6 weeks. Plus PRP after first injection (2 weeks +/- 1 week)and that can be repeated every 12 weeks. Receives: Procedure: Panretinal Photocoagulation (PRP); Drug: Intravitreous injection of pegaptanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Regression of retinal neovascularization
Retinal neovascularization will be measured in disc area units, and progression of neovascularization will be defined as an increasing of 0.5 disc area associated or not with vitreous haemorrhage, and/or pre-retinal haemorrhage, and/or rubeosis, and/or traccional retinal detachment.
Measured: 12-month treatment
Secondary outcomes (8)
Changes from baseline in Best-Corrected Visual Acuity (BCVA)
BCVA will be assessed during the trial (Baseline, Month 3,Month 6, Month 12).
Measured: 12-month treatment
Changes from baseline in macular retinal thickness by Optical Coherent Tomography (OCT)
OCT will be assessed during the trial (Baseline, Month 3, Month 6, Month 12).
Measured: 12-month treatment
Changes from baseline in Visual Fields
Visual Fields will be performed during the trial (Baseline, Month 3, Month 6, Month 12).
Measured: 12-month treatment
Recurrence of retinal neovascularization
To assess if there is recurrence of retinal neovascularization.
Measured: 12-month treatment
Number of treatments needed
To analyse the number of treatments given to each subject during the 12-month treatment.
Measured: 12-month treatment
Additional focal or grid laser for DME
To assess the number of subjects that received additional focal or grid laser for DME.
Measured: 12-month treatment
Adverse events
Drug safety profile.
Measured: 12-month treatment
Need for vitrectomy due to occurrence of vitreous hemorrhage or retinal detachment
To assess the number of subjects who needed vitrectomy due to occurrence of vitreous hemorrhage or retinal detachment.
Measured: 12-month treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2011 (estimated)
- Study startMar 2010
- Primary completionOct 2012
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Risk Proliferative Diabetic RetinopathyStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Association for Innovation and Biomedical Research on Light and Image
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01281098
- Sponsor's protocol ID
- CC-02-2009
- Other IDs
- 2009-016760-36, 2009
- Status last verified
- Apr 2013
- First submitted
- 20 Jan 2011
- Last updated
- 19 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Randomized, Open Label, Phase II Study to Assess Efficacy and Safety of Macugen® (Pegaptanib 0.3 mg Intravitreal Injections) Plus Panretinal Photocoagulation (PRP) and PRP (Monotherapy) in the Treatment of Patients With High Risk Proliferative Diabetic Retinopathy (PDR).
- ClinicalTrials.gov ID
- NCT01281098
- Acronym / sponsor ID
- CC-02-2009
- Conditions
- High Risk Proliferative Diabetic Retinopathy, Diabetes Mellitus Type I, Diabetes Mellitus Type II
- Keywords
- High Risk Proliferative Diabetic Retinopathy, Diabetes Mellitus Type I, Type II, Pegaptanib, Panretinal Photocoagulation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Association for Innovation and Biomedical Research on Light and ImageUniversity, hospital or other
- Study start
- Mar 2010
- Primary completion
- Oct 2012 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 21 Jan 2011 (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.
To evaluate the safety and determine the efficacy of PRP monotherapy or combination therapy (pegaptanib 0.3 mg plus PRP) in patients with Type I or Type II diabetes mellitus and with high risk proliferative diabetic retinopathy.
Detailed description
Panretinal photocoagulation (PRP) can cause regression of retinal neovascularization and reduce the risk of severe vision loss in people with proliferative diabetic retinopathy (PDR). However, this destructive treatment may be associated with side effects (e.g. pain, transient blurring, loss of peripheral and/or night vision, increased risk of macular edema and central vision loss) and it is not always efficient in the regression of the neovascularization.
Vascular endothelial growth factor (VEGF) has been shown to play a role in retinal neovascularization and retinal vascular leakage related with PDR and diabetic macular edema.
Anti-VEGF treatments have been hypothesized as an adjunctive treatment for the management of retinal neovascularization and macular edema related with diabetic retinopathy (DR).
Anti-VEGF agents, such as Macugen®, combined with PRP are expected to control neovascularization without the need for photocoagulation of the posterior pole, around the macula, thus avoiding the major side effects of standard PRP (visual field loss).
A modification of panretinal photocoagulation (PRP) was recently proposed by Madeira et al., (2009) at the 2009 EURETINA Meeting. The described technique involves the progressive application of the DRS photocoagulation rings in a different sequence. First ring: corresponds to the DRS third ring, extruding from the ora serrata to the midperiphery. Second ring: corresponds to DRS second ring, extruding from the midperiphery towards the vortex veins. Third ring: corresponds to DRS first ring, and will only be performed if necessary. This technique resulted in less aggressive visual fields losses by achieving results with only most peripheral photocoagulation. The combination of intravitreal anti-VEGF treatment with pegaptanib, where a series of 3 injections are injected to reverse the neovascularization, while maintaining the macula dry will be completed by the more long term effect of the panretinal photocoagulation. This peripheral photocoagulation proposed is expected to eliminate the chronic VEGF stimulus by eliminating the chronic ischemic factor, while maintaining the visual fields useful for daily activities such as driving, etc.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Panretinal Photocoagulation (PRP) | Active comparator | Procedure: Panretinal Photocoagulation (PRP)Group 1: Panretinal photocoagulation treatment (PRP) at week-0 that can be repeated every 6 weeks. |
| Pegaptanib + Panretinal Photocoagulation (PRP) | Experimental | Procedure: Panretinal Photocoagulation (PRP), Drug: Intravitreous injection of pegaptanibGroup 2: Combination treatment of pegaptanib intravitreous injections at weeks 0, 6 and 12 that can be repeated every 6 weeks. Plus PRP after first injection (2 weeks +/- 1 week)and that can be repeated every 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- High-risk proliferative diabetic retinopathy (HR-PDR) eyes (as defined in section 2).
- BCVA at baseline > 20/320 (25 letters in the ETDRS Chart) in the study eye.
- Clear ocular media and adequate pupillary dilatation to permit good quality fundus photography.
- Intraocular pressure < 21 mmHg.
- Type I, or Type II diabetic subjects as defined by the WHO criteria of either gender, and aged ≥ 18 years.
Key exclusion criteria (30 listed)
- Eyes with prior scatter (panretinal).
- Focal/grid photocoagulation, within the previous 6 months.
- Fibrovascular proliferation with retinal traction.
- Other cause of retinal neovascularization (retinal vein occlusion, radiation retinopathy or others).
- Atrophy/scarring/fibrosis/ hard exudates involving the center of the macula.
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 |
|---|---|---|
| Panretinal Photocoagulation (PRP)Panretinal Photocoagulation (PRP) | Procedure or surgery | Panretinal Photocoagulation (PRP), Pegaptanib + Panretinal Photocoagulation (PRP) |
| Intravitreous injection of pegaptanibIntravitreous injection of pegaptanib | Drug | Pegaptanib + Panretinal Photocoagulation (PRP) |
Primary outcome
Regression of retinal neovascularization
Time frame: 12-month treatment
Retinal neovascularization will be measured in disc area units, and progression of neovascularization will be defined as an increasing of 0.5 disc area associated or not with vitreous haemorrhage, and/or pre-retinal haemorrhage, and/or rubeosis, and/or traccional retinal detachment.
8 secondary outcomes
Changes from baseline in Best-Corrected Visual Acuity (BCVA)
Time frame: 12-month treatment
Changes from baseline in macular retinal thickness by Optical Coherent Tomography (OCT)
Time frame: 12-month treatment
Changes from baseline in Visual Fields
Time frame: 12-month treatment
Recurrence of retinal neovascularization
Time frame: 12-month treatment
Number of treatments needed
Time frame: 12-month treatment
Additional focal or grid laser for DME
Time frame: 12-month treatment
Adverse events
Time frame: 12-month treatment
Need for vitrectomy due to occurrence of vitreous hemorrhage or retinal detachment
Time frame: 12-month treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2015.
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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 2 study testing Panretinal Photocoagulation (PRP) and Intravitreous injection of pegaptanib in people with High Risk Proliferative Diabetic Retinopathy and Diabetes Mellitus Type I, run by Association for Innovation and Biomedical Research on Light and Image at 1 site in Portugal.
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 8 inclusion and 30 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: finished, as of the sponsor's last update on 19 Mar 2015. 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 Portugal. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Regression of retinal neovascularization (time frame: 12-month treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Mar 2015; AzTrials last refreshed its copy on 28 Oct 2026.