Diabetic RetinopathyNCT02590094
Preoperative Bevacizumab and Ziv-Aflibercept Administration in PDR Subjects Undergoing PPV
A study testing Intravitreal bevacizumab or intravitreal ziv-aflibercept in people with Diabetic Retinopathy, run by Panhandle Eye Group, LLP at 1 site in Mexico.
Trial summary
To compare outcomes in subjects receiving different doses and treatment intervals of intravitreal bevacizumab or ziv-aflibercept preoperatively administered prior to undergoing vitrectomy for complications of proliferative diabetic retinopathy. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Diabetic Retinopathy
- What is being tested?
- Intravitreal bevacizumab or intravitreal ziv-aflibercept
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 568 participants
- Where
- 1 siteMexico
- Study dates
- Oct 2015to 4 Jan 2019
- Phase
- Interventional
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject age is 18-85 years.
- Subject consents to study participation and is capable of 6 months of follow-up.
- The subject has type I or II Diabetes Mellitus with active PDR in the study eye.
- Best-corrected spectacle visual acuity (BCSVA) on the Snellen eye chart ranges from 20/40 to light perception with projection in the study eye.
- The subject is determined to need a PPV because of reduced BCSVA principally from a non-clearing vitreous hemorrhage, TRD, fibrous proliferation, or a combination of the three. When non-clearing vitreous hemorrhage is the principal reason for PPV, the hemorrhage must have been present by subjective history for at least 3 months. When TRD is the principal reason for PPV, the TRD must be threatening (within one disc diameter) or involving the fovea. When fibrovascular proliferation is the principal reason for PPV, it must be extensive (>3 clock hours) and threatening (within one disc diameter) or involving the fovea.
- Only one eye per patient is eligible for the study.
Who cannot join
- Subject is known to have a significant retinal/optic nerve disease otherwise unrelated to Diabetes Mellitus, which in the opinion of the examiner is responsible for two or more lines of reduced BCSVA (macular degeneration, optic neuritis, glaucoma, amblyopia, etc.) in the study eye.
- Subject is known to have macular ischemia, which in the opinion of the examiner, is responsible for two or more lines of reduced BCSVA in the study eye.
- Subject has a significant corneal opacity, which in the opinion of the examiner, is responsible for two or more lines of reduced BCSVA (corneal scar, ectasia, etc.) in the study eye.
- Subject is known to have had a macula-involving retinal detachment for greater than 6 months in the study eye.
- Subject has had a previous vitrectomy (anterior or PPV) in the study eye.
- Subject has uncontrolled neovascular glaucoma (intraocular pressure > 30 mmHg despite medical/surgical treatment) in the study eye.
- Subject received systemic or intravitreal anti-VEGF treatment to the study eye within 3 months of anticipated study enrollment.
- Subject has uncontrolled hypertension (systolic > 200 mmHg or diastolic > 120 mmHg) despite adherence to a multiple anti-hypertensive medication regimen.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of Interval Variation and Dosage in Preoperative Bevacizumab and Ziv-Aflibercept Administration in Proliferative Diabetic Retinopathy Undergoing Vitrectomy
To compare outcomes in subjects receiving different doses and treatment intervals of intravitreal bevacizumab or ziv-aflibercept preoperatively administered prior to undergoing vitrectomy for complications of proliferative diabetic retinopathy.
Read the detailed description
Severe vision loss in patients with proliferative diabetic retinopathy (PDR) frequently results from complications related to neovascularization and fibrovascular proliferation. Patients with PDR are typically considered candidates for pars plana vitrectomy (PPV) when non-clearing vitreous hemorrhaging, tractional retinal detachment (TRD) development or extensive fibrovascular proliferation occur. Visual prognosis is guarded in patients undergoing PPV with these advanced presentations of PDR because of the high rate of both intra-operative and postoperative complications. Intra-operative bleeding may result in poor visualization during PPV that increases total surgery time and ultimately leads to surgical failure, while recurrent/persistent postoperative vitreous hemorrhage may occur as high as 75% and hinder visual rehabilitation and monitoring of further disease progression.
Preoperative administration of bevacizumab (Avastin; Genentech, Inc, South San Francisco, California, USA), a full-length recombinant humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), has been reported in prospective clinical trials to decrease the overall surgery time, lower the rate of intra-operative complications, and reduce the occurrence of postoperative hemorrhaging in PDR patients with active neovascularization and/or extensive fibrovascular proliferation undergoing PPV. Furthermore, two meta-analysis studies examining published randomized controlled trials support the use of intravitreal bevacizumab (IVB) as a preoperative adjunct. Although IVB is widely used as a preoperative adjunct in patients with PDR undergoing PPV, little clinical data is available regarding the optimal timing of preoperative IVB administration or the most effective dose. In this randomized clinical study, we attempt to elucidate the most appropriate interval and dose for the administration of preoperative IVB in patients with PDR undergoing PPV for non-clearing vitreous hemorrhaging, TRD or extensive fibrovascular proliferation.
Ziv-aflibercept (Zaltrap, Regeneron) is a recombinant fusion protein that acts as a soluble decoy receptor and binds to VEGF-A, VEGF-B, and placental growth factor, similar to aflibercept (Eylea, Regeneron, Tarrytown, NY), which is FDA approved for intravitreal administration to treat various retinal diseases. At the dose of 1.25 mg/0.05 mL, ziv-aflibercept has been reported to safely and effectively treat neovascular macular degeneration and diabetic macular edema, similar in efficacy to bevacizumab. Presently, there are no reports regarding the effectiveness of preoperative ziv-aflibercept administration prior to PPV for PDR. In this randomized clinical trial, we also evaluate the effectiveness of ziv-aflibercept to bevacizumab, and attempt to elucidate the most appropriate interval for the administration of preoperative ziv-aflibercept in patients with PDR undergoing PPV for non-clearing vitreous hemorrhaging, TRD or extensive fibrovascular proliferation.
- Conditions
- Diabetic Retinopathy
- Being tested
- Intravitreal bevacizumab or intravitreal ziv-aflibercept
- Medical subject headings
- Diabetic Retinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravitreal bevacizumab or intravitreal ziv-afliberceptDrug
Intravitreal bevacizumab or intravitreal ziv-aflibercept is given preoperatively at various time intervals and doses.
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Study Group A: Subjects receive 2.5 mg intravitreal bevacizumab 1-3 days prior to vitrectomy. Receives: Drug: Intravitreal bevacizumab or intravitreal ziv-aflibercept |
| B | Active comparator | Study Group B: Subjects receive 2.5 mg intravitreal bevacizumab 5-10 days prior to vitrectomy. Receives: Drug: Intravitreal bevacizumab or intravitreal ziv-aflibercept |
| C | Active comparator | Study Group C: Subjects receive 1.25 mg intravitreal bevacizumab 1-10 days prior to vitrectomy. Receives: Drug: Intravitreal bevacizumab or intravitreal ziv-aflibercept |
| D | Active comparator | Study Group D: Subjects receive 0.625 mg intravitreal bevacizumab 1-10 days prior to vitrectomy. Receives: Drug: Intravitreal bevacizumab or intravitreal ziv-aflibercept |
| E | Active comparator | Study Group E: Subjects receive 2.5 mg intravitreal bevacizumab 1-10 days prior to vitrectomy. Receives: Drug: Intravitreal bevacizumab or intravitreal ziv-aflibercept |
| F | Active comparator | Study Group F: Subjects receive 1.25 mg intravitreal ziv-aflibercept 1-10 days prior to vitrectomy. Receives: Drug: Intravitreal bevacizumab or intravitreal ziv-aflibercept |
| G | Active comparator | Study Group G: Subjects receive 1.25 mg intravitreal ziv-aflibercept 1-3 days prior to vitrectomy. Receives: Drug: Intravitreal bevacizumab or intravitreal ziv-aflibercept |
| H | Active comparator | Study Group H: Subjects receive 1.25 mg intravitreal ziv-aflibercept 5-10 days prior to vitrectomy. Receives: Drug: Intravitreal bevacizumab or intravitreal ziv-aflibercept |
| I | Active comparator | Study Group I: Subjects receive 1.25 mg intravitreal ziv-aflibercept 1-10 days prior to vitrectomy, and then receive 1.25 mg intravitreal ziv-aflibercept at the completion of the vitrectomy. Receives: Drug: Intravitreal bevacizumab or intravitreal ziv-aflibercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Acuity
Change in BCSVA from baseline
Measured: 6 months
Secondary outcomes (2)
Complications
Rate of complications (intra-operative and postoperative)
Measured: 6 months
Time
Total surgery time
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2015 (estimated)
- Study startOct 2015
- Primary completion4 Jan 2019
- Study completion4 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 568 participants (actual)
Sponsor and investigators
- Lead sponsor
- Panhandle Eye Group, LLP
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sloan W. Rush, MD, Panhandle Eye Group, LLP
- Investigators
- Sloan Rush, MD, Study chair, panhandle eye group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02590094
- Sponsor's protocol ID
- 4
- Status last verified
- Nov 2021
- First submitted
- 27 Oct 2015
- Last updated
- 3 Dec 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Interval Variation and Dosage in Preoperative Bevacizumab and Ziv-Aflibercept Administration in Proliferative Diabetic Retinopathy Undergoing Vitrectomy
- ClinicalTrials.gov ID
- NCT02590094
- Acronym / sponsor ID
- 4
- Conditions
- Diabetic Retinopathy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 568 participants (actual)
- Lead sponsor
- Panhandle Eye Group, LLPUniversity, hospital or other
- Study start
- Oct 2015 (actual)
- Primary completion
- 4 Jan 2019 (actual)
- Study completion
- 4 Jan 2019 (actual)
- First posted
- 28 Oct 2015 (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 compare outcomes in subjects receiving different doses and treatment intervals of intravitreal bevacizumab or ziv-aflibercept preoperatively administered prior to undergoing vitrectomy for complications of proliferative diabetic retinopathy.
Detailed description
Severe vision loss in patients with proliferative diabetic retinopathy (PDR) frequently results from complications related to neovascularization and fibrovascular proliferation. Patients with PDR are typically considered candidates for pars plana vitrectomy (PPV) when non-clearing vitreous hemorrhaging, tractional retinal detachment (TRD) development or extensive fibrovascular proliferation occur. Visual prognosis is guarded in patients undergoing PPV with these advanced presentations of PDR because of the high rate of both intra-operative and postoperative complications. Intra-operative bleeding may result in poor visualization during PPV that increases total surgery time and ultimately leads to surgical failure, while recurrent/persistent postoperative vitreous hemorrhage may occur as high as 75% and hinder visual rehabilitation and monitoring of further disease progression.
Preoperative administration of bevacizumab (Avastin; Genentech, Inc, South San Francisco, California, USA), a full-length recombinant humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), has been reported in prospective clinical trials to decrease the overall surgery time, lower the rate of intra-operative complications, and reduce the occurrence of postoperative hemorrhaging in PDR patients with active neovascularization and/or extensive fibrovascular proliferation undergoing PPV. Furthermore, two meta-analysis studies examining published randomized controlled trials support the use of intravitreal bevacizumab (IVB) as a preoperative adjunct. Although IVB is widely used as a preoperative adjunct in patients with PDR undergoing PPV, little clinical data is available regarding the optimal timing of preoperative IVB administration or the most effective dose. In this randomized clinical study, we attempt to elucidate the most appropriate interval and dose for the administration of preoperative IVB in patients with PDR undergoing PPV for non-clearing vitreous hemorrhaging, TRD or extensive fibrovascular proliferation.
Ziv-aflibercept (Zaltrap, Regeneron) is a recombinant fusion protein that acts as a soluble decoy receptor and binds to VEGF-A, VEGF-B, and placental growth factor, similar to aflibercept (Eylea, Regeneron, Tarrytown, NY), which is FDA approved for intravitreal administration to treat various retinal diseases. At the dose of 1.25 mg/0.05 mL, ziv-aflibercept has been reported to safely and effectively treat neovascular macular degeneration and diabetic macular edema, similar in efficacy to bevacizumab. Presently, there are no reports regarding the effectiveness of preoperative ziv-aflibercept administration prior to PPV for PDR. In this randomized clinical trial, we also evaluate the effectiveness of ziv-aflibercept to bevacizumab, and attempt to elucidate the most appropriate interval for the administration of preoperative ziv-aflibercept in patients with PDR undergoing PPV for non-clearing vitreous hemorrhaging, TRD or extensive fibrovascular proliferation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: Intravitreal bevacizumab or intravitreal ziv-afliberceptStudy Group A: Subjects receive 2.5 mg intravitreal bevacizumab 1-3 days prior to vitrectomy. |
| B | Active comparator | Drug: Intravitreal bevacizumab or intravitreal ziv-afliberceptStudy Group B: Subjects receive 2.5 mg intravitreal bevacizumab 5-10 days prior to vitrectomy. |
| C | Active comparator | Drug: Intravitreal bevacizumab or intravitreal ziv-afliberceptStudy Group C: Subjects receive 1.25 mg intravitreal bevacizumab 1-10 days prior to vitrectomy. |
| D | Active comparator | Drug: Intravitreal bevacizumab or intravitreal ziv-afliberceptStudy Group D: Subjects receive 0.625 mg intravitreal bevacizumab 1-10 days prior to vitrectomy. |
| E | Active comparator | Drug: Intravitreal bevacizumab or intravitreal ziv-afliberceptStudy Group E: Subjects receive 2.5 mg intravitreal bevacizumab 1-10 days prior to vitrectomy. |
| F | Active comparator | Drug: Intravitreal bevacizumab or intravitreal ziv-afliberceptStudy Group F: Subjects receive 1.25 mg intravitreal ziv-aflibercept 1-10 days prior to vitrectomy. |
| G | Active comparator | Drug: Intravitreal bevacizumab or intravitreal ziv-afliberceptStudy Group G: Subjects receive 1.25 mg intravitreal ziv-aflibercept 1-3 days prior to vitrectomy. |
| H | Active comparator | Drug: Intravitreal bevacizumab or intravitreal ziv-afliberceptStudy Group H: Subjects receive 1.25 mg intravitreal ziv-aflibercept 5-10 days prior to vitrectomy. |
| I | Active comparator | Drug: Intravitreal bevacizumab or intravitreal ziv-afliberceptStudy Group I: Subjects receive 1.25 mg intravitreal ziv-aflibercept 1-10 days prior to vitrectomy, and then receive 1.25 mg intravitreal ziv-aflibercept at the completion of the vitrectomy. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Subject age is 18-85 years.
- Subject consents to study participation and is capable of 6 months of follow-up.
- The subject has type I or II Diabetes Mellitus with active PDR in the study eye.
- Best-corrected spectacle visual acuity (BCSVA) on the Snellen eye chart ranges from 20/40 to light perception with projection in the study eye.
- The subject is determined to need a PPV because of reduced BCSVA principally from a non-clearing vitreous hemorrhage, TRD, fibrous proliferation, or a combination of the three. When non-clearing vitreous hemorrhage is the principal reason for PPV, the hemorrhage must have been present by subjective history for at least 3 months. When TRD is the principal reason for PPV, the TRD must be threatening (within one disc diameter) or involving the fovea. When fibrovascular proliferation is the principal reason for PPV, it must be extensive (>3 clock hours) and threatening (within one disc diameter) or involving the fovea.
Key exclusion criteria (8 listed)
- Subject is known to have a significant retinal/optic nerve disease otherwise unrelated to Diabetes Mellitus, which in the opinion of the examiner is responsible for two or more lines of reduced BCSVA (macular degeneration, optic neuritis, glaucoma, amblyopia, etc.) in the study eye.
- Subject is known to have macular ischemia, which in the opinion of the examiner, is responsible for two or more lines of reduced BCSVA in the study eye.
- Subject has a significant corneal opacity, which in the opinion of the examiner, is responsible for two or more lines of reduced BCSVA (corneal scar, ectasia, etc.) in the study eye.
- Subject is known to have had a macula-involving retinal detachment for greater than 6 months in the study eye.
- Subject has had a previous vitrectomy (anterior or PPV) 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 |
|---|---|---|
| Intravitreal bevacizumab or intravitreal ziv-afliberceptIntravitreal bevacizumab or intravitreal ziv-aflibercept is given preoperatively at various time intervals and doses. | Drug | A, B, C, D, E, F, G, H, I |
Primary outcome
Visual Acuity
Time frame: 6 months
Change in BCSVA from baseline
2 secondary outcomes
Complications
Time frame: 6 months
Time
Time frame: 1 day
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 3 Dec 2021.
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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.
Sloan Rush, MD study chair
panhandle eye group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intravitreal bevacizumab or intravitreal ziv-aflibercept in people with Diabetic Retinopathy, run by Panhandle Eye Group, LLP at 1 site in Mexico.
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 6 inclusion and 8 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 3 Dec 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 Mexico. 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.
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?
Visual Acuity (time frame: 6 months). 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 3 Dec 2021.