Retinopathy, DiabeticPhase 4PRAVANCT04702048
Evaluation of the Retina in Patients With Non-proliferative Diabetic Retinopathy After Aflibercept Injection in the Eye
A Phase 4 study testing Aflibercept Injection in people with Retinopathy, Diabetic, run by University of Rochester at 1 site in United States.
Trial summary
The purpose of this study is to specifically assess the effect of intravitreal aflibercept injections on the health of cells and the flow of blood through the retinal blood vessels by using advanced technology called adaptive optics. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Retinopathy, Diabetic
- What is being tested?
- Aflibercept Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2021to 1 Feb 2024
- 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
- Documented Type 1 or 2 diabetes mellitus who have moderately severe to severe NPDR (DRSS levels 47 or 53) as confirmed by 2 independent physician evaluators.
- Age ≥18 years
- Willingness and the ability to provide signed informed consent, comply with clinic visits and study-related procedure, and provide Health Insurance Portability and Accountability Act authorization
- BCVA of ≥ 73 letters, inclusive (≥20/40 approximate Snellen equivalent), using the ETDRS protocol at the initial testing distance of 4 meters (see the BCVA manual for additional details) on Day 1
- Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition of good quality CFPs (including ETDRS 7 modified fields or Optos ultra-widefield image to permit grading of diabetic retinopathy and assessment of the retina) and other imaging modalities, including AOSLO.
- No center-involved macular edema (defined as fluid within 1000 microns of the fovea)
- HbA1c of ≤10% within 2 months prior to the first injection visit date
- For men* and women** of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 3 months after the final dose of study treatment. Adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly. Contraception is not required for men with documented vasectomy. Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
Who cannot join
- Presence of DME threatening the center of the macula (within 1,000 microns of the foveal center) in the study eye
- Evidence of retinal neovascularization on clinical examination or FA
- Any prior focal or grid laser photocoagulation (within 1,000 microns of the foveal center) or any prior PRP in the study eye
- Any prior systemic anti-VEGF treatment or IVT anti-VEGF treatment in the study eye
- Any prior intraocular steroid injection in the study eye
- History of vitreoretinal surgery in the study eye
Show all 21Show fewer
- Intraocular pressure (IOP) ≥25 mm Hg in the study eye
- Evidence of active infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye
- Any intraocular inflammation or infection in either eye within 3 months of the screening visit
- Current Anterior segment neovascularization, vitreous hemorrhage, or tractional retinal detachment visible at the screening assessments in the study eye
- Ocular media of insufficient quality to obtain fundus and optical coherence tomography (OCT), and adaptive optics images in the study eye
- Hemoglobin A1c (HbA1c) >12%, or if HbA1c is ≤12%, diabetes mellitus is uncontrolled in the opinion of the investigator
- Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the patient beyond what is to be expected from standard procedures of IVT injections, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety
- Uncontrolled blood pressure (defined as systolic >160 mm Hg or diastolic >95 mm Hg while patient is sitting)
- History of cerebrovascular accident or myocardial infarction within 6 months of day 1
- Renal failure, dialysis, or history of renal transplant
- Positive serum hCG/urine pregnancy test at the screening or baseline visit
- History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk for treatment complications
- Participation as a patient in any interventional ocular clinical study within the 12 weeks prior to day 1 of the study
- Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception prior to the initial dose/start of the first treatment, during the study, and for at least 3 months after the last dose. Adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly. Contraception is not required for men with documented vasectomy.
- Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Flaum Eye Institute, University of Rochester Medical Center
Rochester, New York, 14642
About this study
Official title: The Evaluation of Retinal PhotoReceptors And Vasculature in Moderate and Severe Non-proliferative Diabetic Retinopathy Patients After Intravitreal Aflibercept on Using Adaptive Optics Imaging Study (PRAVA) Study
The purpose of this study is to specifically assess the effect of intravitreal aflibercept injections on the health of cells and the flow of blood through the retinal blood vessels by using advanced technology called adaptive optics.
- Conditions
- Retinopathy, Diabetic
- Being tested
- Aflibercept Injection, Sham injection
- Medical subject headings
- Diabetic Retinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aflibercept InjectionDrug
Patients randomized to Arm A will receive 2 mg IVT aflibercept injections every 4 weeks (Q4W) to Week 20, followed by 2-mg aflibercept injections Q8W to Week 52.
Sham injectionDrug
Patients randomized to Arm B will receive sham intravitreal injections every 4 weeks (Q4W) to Week 20, followed by sham intravitreal injections Q8W to Week 52. Sham means eye will be numbed and a syringe with no needle will be touched to the eye.
| Study group | Role | What they receive |
|---|---|---|
| Aflibercept injection | Experimental | Intravitreal injection of Aflibercept Receives: Drug: Aflibercept Injection |
| Sham injection | Placebo comparator | Empty syringe with no needle Receives: Drug: Sham injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change in photoreceptor mosaic
Adaptive optics imaging will be used to visualize the photoreceptor cells in the eye and the number of photoreceptor cells will be quantified at baseline and 52 weeks.
Measured: baseline to 52 weeks
Mean change in photoreceptor cell density
Adaptive optics imaging will be used to visualize the photoreceptor cells in the eye and the number of photoreceptor cells per square micron of image will be quantified at baseline and 52 weeks.
Measured: baseline to 52 weeks
Mean change in photoreceptor cell spacing
Adaptive optics imaging will be used to visualize the photoreceptor cells in the eye and a measurement of the space between photoreceptor cells will be calculated at baseline and 52 weeks.
Measured: baseline to 52 weeks
Secondary outcomes (21)
Percent of participants with any ocular adverse events
Measured: 52 weeks
Percent of participants with a severe ocular adverse events
Measured: 52 weeks
Percent of participants with a non-ocular adverse events
Measured: 52 weeks
Percent of participants with a severe non-ocular adverse events
Measured: 52 weeks
Mean change in foveal avascular zone area
Adaptive optics and optical coherence tomography angiography will be used to quantify the area of the macula without blood vessels.
Measured: baseline to 52 weeks
Mean change in macular retina non-perfusion area
Optical coherence tomography angiography will be used to quantify the area of the macula without blood vessels.
Measured: baseline to 52 weeks
Mean change in capillary blood cell velocity
Adaptive optics will be used to quantify the mean speed of blood cells passing through the retinal blood vessels.
Measured: baseline to 52 weeks
Mean change in blood cell flux
Adaptive optics will be used to quantify the mean number o blood cells passing through the blood vessel per period of time.
Measured: baseline to 52 weeks
Mean change in number of capillary occlusions
Adaptive optics will be used to quantify the number of time blood flow stops (occlusions) in the eye blood vessels.
Measured: baseline to 52 weeks
Change in duration of capillary occlusions
Adaptive optics will be used to quantify the length of time blood flow stops (occlusions) in the eye blood vessels.
Measured: baseline to 52 weeks
Proportion of patients with a ≥ 2-step DRS improvement from baseline on the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale (ETDRS DRSS)
The ETDRS DRSS measures the number of vascular changes seen in the eye due to diabetes. The range is 10-81. A lower value indicates a better health outcome. The steps cut offs are 10, 20, 35, 43, 47, 53, 60, 61, 65, 71, 75, 81.
Measured: 52 weeks
Proportion of patients with a ≥ 3-step DRS improvement from baseline on the ETDRS DRSS.
The ETDRS DRSS measures the number of vascular changes seen in the eye due to diabetes. The range is 10-81. A lower value indicates a better health outcome. The steps cut offs are 10, 20, 35, 43, 47, 53, 60, 61, 65, 71, 75, 81.
Measured: 52 weeks
Proportion of participants developing a vision-threatening complication due to diabetic retinopathy
Progression to proliferative diabetic retinopathy, develop of diabetic macular edema, development of neovascular glaucoma and vitrous hemorrhage are all vision-threatening complications.
Measured: 52 weeks
Mean change in central subfield thickness
Optical coherence tomography will be used to measure the central subfield thickness.
Measured: baseline to 52 weeks
Proportion of patients with absence of intraretinal fluid
Optical coherence tomography will be used to measure presence or absence of intraretinal fluid.
Measured: 52 weeks
Proportion of patients with absence of subretinal fluid
Optical coherence tomography will be used to measure presence or absence of intraretinal fluid.
Measured: 52 weeks
Mean change in mean parafoveal macular ganglion cell layer and inner plexiform layer (mGCIPL) thickness
Optical coherence tomography will be used to measure mGCIPL thickness.
Measured: baseline to 52 weeks
Mean change in Best Corrected Visual Acuity (BCVA)
BCVA is a visual test using letters and change will be measured as the number of letters correctly read.
Measured: baseline to 52 weeks
Change in proportion of patients with BCVA Snellen equivalent of 20/40 or better
Measured: baseline to 52 weeks
Proportion of participants who receive panretinal photocoagulation (PRP)
PRP is a laser procedure for proliferative diabetic retinopathy that will be performed based on clinical evaluation of the patient.
Measured: week 52
Proportion of participants who receive intravitreal aflibercept
Measured: week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2021
- Study start1 Feb 2021 (estimated)
- Primary completion1 Feb 2024 (estimated)
- Study completion1 Feb 2024 (estimated)
Why it stopped: sponsor withdrew funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Retinopathy, DiabeticStudies of the same condition, open and under way.
- More trials run by University of RochesterThe 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
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jesse Schallek, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04702048
- Sponsor's protocol ID
- STUDY00005589
- Acronym
- PRAVA
- Status last verified
- Apr 2021
- First submitted
- 6 Jan 2021
- Last updated
- 5 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Evaluation of Retinal PhotoReceptors And Vasculature in Moderate and Severe Non-proliferative Diabetic Retinopathy Patients After Intravitreal Aflibercept on Using Adaptive Optics Imaging Study (PRAVA) Study
- ClinicalTrials.gov ID
- NCT04702048
- Acronym / sponsor ID
- PRAVA / STUDY00005589
- Conditions
- Retinopathy, Diabetic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: sponsor withdrew funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Study start
- 1 Feb 2021 (estimated)
- Primary completion
- 1 Feb 2024 (estimated)
- Study completion
- 1 Feb 2024 (estimated)
- First posted
- 8 Jan 2021 (actual)
- 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.
The purpose of this study is to specifically assess the effect of intravitreal aflibercept injections on the health of cells and the flow of blood through the retinal blood vessels by using advanced technology called adaptive optics.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aflibercept injection | Experimental | Drug: Aflibercept InjectionIntravitreal injection of Aflibercept |
| Sham injection | Placebo comparator | Drug: Sham injectionEmpty syringe with no needle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Documented Type 1 or 2 diabetes mellitus who have moderately severe to severe NPDR (DRSS levels 47 or 53) as confirmed by 2 independent physician evaluators.
- Age ≥18 years
- Willingness and the ability to provide signed informed consent, comply with clinic visits and study-related procedure, and provide Health Insurance Portability and Accountability Act authorization
- BCVA of ≥ 73 letters, inclusive (≥20/40 approximate Snellen equivalent), using the ETDRS protocol at the initial testing distance of 4 meters (see the BCVA manual for additional details) on Day 1
- Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition of good quality CFPs (including ETDRS 7 modified fields or Optos ultra-widefield image to permit grading of diabetic retinopathy and assessment of the retina) and other imaging modalities, including AOSLO.
Key exclusion criteria (21 listed)
- Presence of DME threatening the center of the macula (within 1,000 microns of the foveal center) in the study eye
- Evidence of retinal neovascularization on clinical examination or FA
- Any prior focal or grid laser photocoagulation (within 1,000 microns of the foveal center) or any prior PRP in the study eye
- Any prior systemic anti-VEGF treatment or IVT anti-VEGF treatment in the study eye
- Any prior intraocular steroid injection in the study eye
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 |
|---|---|---|
| Aflibercept InjectionPatients randomized to Arm A will receive 2 mg IVT aflibercept injections every 4 weeks (Q4W) to Week 20, followed by 2-mg aflibercept injections Q8W to Week 52. | Drug | Aflibercept injection |
| Sham injectionPatients randomized to Arm B will receive sham intravitreal injections every 4 weeks (Q4W) to Week 20, followed by sham intravitreal injections Q8W to Week 52. Sham means eye will be numbed and a syringe with no needle will be touched to the eye. | Drug | Sham injection |
Primary outcome
Mean change in photoreceptor mosaic
Time frame: baseline to 52 weeks
Adaptive optics imaging will be used to visualize the photoreceptor cells in the eye and the number of photoreceptor cells will be quantified at baseline and 52 weeks.
Mean change in photoreceptor cell density
Time frame: baseline to 52 weeks
Adaptive optics imaging will be used to visualize the photoreceptor cells in the eye and the number of photoreceptor cells per square micron of image will be quantified at baseline and 52 weeks.
Mean change in photoreceptor cell spacing
Time frame: baseline to 52 weeks
Adaptive optics imaging will be used to visualize the photoreceptor cells in the eye and a measurement of the space between photoreceptor cells will be calculated at baseline and 52 weeks.
21 secondary outcomes
Percent of participants with any ocular adverse events
Time frame: 52 weeks
Percent of participants with a severe ocular adverse events
Time frame: 52 weeks
Percent of participants with a non-ocular adverse events
Time frame: 52 weeks
Percent of participants with a severe non-ocular adverse events
Time frame: 52 weeks
Mean change in foveal avascular zone area
Time frame: baseline to 52 weeks
Mean change in macular retina non-perfusion area
Time frame: baseline to 52 weeks
Mean change in capillary blood cell velocity
Time frame: baseline to 52 weeks
Mean change in blood cell flux
Time frame: baseline to 52 weeks
Mean change in number of capillary occlusions
Time frame: baseline to 52 weeks
Change in duration of capillary occlusions
Time frame: baseline to 52 weeks
Proportion of patients with a ≥ 2-step DRS improvement from baseline on the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale (ETDRS DRSS)
Time frame: 52 weeks
Proportion of patients with a ≥ 3-step DRS improvement from baseline on the ETDRS DRSS.
Time frame: 52 weeks
Proportion of participants developing a vision-threatening complication due to diabetic retinopathy
Time frame: 52 weeks
Mean change in central subfield thickness
Time frame: baseline to 52 weeks
Proportion of patients with absence of intraretinal fluid
Time frame: 52 weeks
Proportion of patients with absence of subretinal fluid
Time frame: 52 weeks
Mean change in mean parafoveal macular ganglion cell layer and inner plexiform layer (mGCIPL) thickness
Time frame: baseline to 52 weeks
Mean change in Best Corrected Visual Acuity (BCVA)
Time frame: baseline to 52 weeks
Change in proportion of patients with BCVA Snellen equivalent of 20/40 or better
Time frame: baseline to 52 weeks
Proportion of participants who receive panretinal photocoagulation (PRP)
Time frame: week 52
Proportion of participants who receive intravitreal aflibercept
Time frame: week 52
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2021.
- Individual participant dataSharing planned: Undecided
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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 Aflibercept Injection in people with Retinopathy, Diabetic, run by University of Rochester at 1 site in United States.
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 21 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: withdrawn, as of the sponsor's last update on 5 May 2021. 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 United States. 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. Some participants in this study may receive a placebo. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Mean change in photoreceptor mosaic (time frame: baseline to 52 weeks). The study lists 3 primary outcomes in all. 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 5 May 2021.