Retinopathy of PrematurityPhase 2BLOCK-ROPNCT01232777
Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity (BLOCK-ROP)
A Phase 2 study testing Bevacizumab in people with Retinopathy of Prematurity, run by Vision Research Foundation at 19 sites in 2 countries.
Trial summary
The purpose of this study is to determine whether a single intravitreal (into the gel of the eye) injection of Avastin 0.625mg or 0.75mg is equivalent (non-inferior) to treatment with standard of care laser in infants with Type I pre-threshold retinopathy of prematurity (ROP) diagnosed at 30-36 weeks gestational age. Read more about this study
- Who is it for?
- Ages 30 to 36 weeks
- Conditions the study is for
- Retinopathy of Prematurity
- What is being tested?
- Bevacizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 19 sitesin 2 countries
- Study dates
- Jun 2012to Jul 2018
- 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 30 to 36 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Inborn babies at participating NICU's who meet inclusion criteria
- Outborn babies transferred to participating NICU's who meet inclusion criteria
- Type 1 pre-threshold ROP
- No prior treatment
- Post menstrual age less than 36 1/7 weeks
- Post menstrual age greater than 30 weeks
Who cannot join
- Fatal systemic anomaly
- An ocular anomaly of one or both eye affecting the retina or choroid
- An ocular anomaly precluding use of the RetCam (ex., microphthalmia)
- Neonatologist feels inclusion will unduly challenge the infant
- Refusal of initial consent
- Refusal of subsequent evaluation
- Media opacity precluding fundus visualization (ex., cataract)
- Any ocular or periocular infection(s)
Trial locations and contacts
19 sites in 2 countries.
19 sites in 2 countries
United States18 sites
Emory Eye Center
Atlanta, Georgia, 30322
Austin Retina Associates
Austin, Texas, 78705
Children's Hospital, Dept. of Ophthalmology
Boston, Massachusetts, 02115
Abrahamson Pediatric Eye Institute, Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Cleveland Clinic
Cleveland, Ohio, 44105
Midwest Retina
Dublin, Ohio, 43016
Texas Children's Hospital
Houston, Texas, 77030
Children's Hospital Los Angeles
Los Angeles, California, 90027
Jules Stein Eye Institute, UCLA
Los Angeles, California, 90095
University Hospitals Eye Insitute, Rainbow Babies & Children's Hospital
Mayfield Heights, Ohio, 44134
Bascon Palmer Eye Institute
Miami, Florida, 33136
Medical College of Wisconsin--Eye Insititute
Milwaukee, Wisconsin, 53266
Department of Ophthalmology, Weill Cornell Medical College
New York, New York, 10021
Insitute of Ophthalmology and Medical Science, New Jersey Medical School
Newark, New Jersey, 07103
Eye Insitute at Stanford
Palo Alto, California, 94303
St. Christopher's Hospital for Children, Drexel Univ. School of Medicine
Philadelphia, Pennsylvania, 19134
Associated Retinal Consultants/William Beaumont Hospital
Royal Oak, Michigan, 48073
University of Utah, Moran Eye Center
Salt Lake City, Utah, 84132
About this study
The purpose of this study is to determine whether a single intravitreal (into the gel of the eye) injection of Avastin 0.625mg or 0.75mg is equivalent (non-inferior) to treatment with standard of care laser in infants with Type I pre-threshold retinopathy of prematurity (ROP) diagnosed at 30-36 weeks gestational age.
Read the detailed description
Retinopathy of Prematurity (ROP) is a leading cause of blindness in children in developed countries around the world, and an increasing cause of blindness in developing countries.
The retina lines the inside of the eye. It functions as "film" within the camera, which is the eye. When an infant is born prematurely, the vascular network necessary to nourish the retina has not fully developed. As a consequence, in some infants abnormal vessels grow instead of the normal ones--a condition known as ROP. The abnormal vessels carry scar tissue along with them, and may lead to retinal detachment and blindness if the eye is not treated.
The multi-center trial of Cryotherapy for Retinopathy of Prematurity (CRYo-ROP) Study demonstrated that ablation of the peripheral avascular retina reduced the risk of poor structural and visual outcome due to retinal distortion or detachment in ROP (1980's). The ablated retina is not functional and is not amendable to regeneration.
Peripheral retinal ablation is not universally effective in fostering regression of ROP. This is particularly true for an aggressive form of ROP (aggressive posterior ROP, or APROP), which typically afflicts profoundly premature and sick neonates. In this subset of infants, progression of ROP to retinal detachments in both eyes and even blindness may occur despite timely and complete peripheral retinal laser ablation.
RATIONALE:
The development of ROP is largely dependant on vascular endothelial growth factor (VEGF). When an infant is born prematurely, the relatively hyperoxic environment that the baby is introduced to shuts down the production of VEGF. Retinal maturation is thus delayed. Subsequently, at a time when intraocular VEGF levels would be declining late in the third trimester of pregnancy, abnormally high levels of VEGF are seen due to large areas of avascular retina and associated tissue hypoxia.
The availability of FDA-approved drugs for anti-VEGF treatment renders it possible to treat such eye off-label. Available drugs include pegaptanib sodium (Macugen) for partial blockage of VEGF-A, or drugs such a ranibizumab (Lucentis) and bevacizumab (Avastin), which cause complete blockage of VEGF-A.
As VEGF is required in the developing retina for normal angiogenesis, and our goal is not to penetrate tissue, but to block the excessive levels of VEGF trapped within the overlying vitreous which is responsible for the abnormal vasculature in ROP.
For purposes of this study, we have chosen bevacizumab (Avastin) which will: a) attain complete blockage (vs. Macugen) of intravitreal VEGF-A, and b)which is limited in its ability to penetrate tissues because it is a full antibody (vs. Lucentis, an antibody fragment specifically designed for better tissue penetration), and is more likely to restore VEGF homeostasis within the developing retina.
- Conditions
- Retinopathy of Prematurity
- Being tested
- Bevacizumab
- Keywords
- Retinopathy of Prematurity, Bevacizumab, Avastin, Vascular Endothelial Growth Factor
- Medical subject headings
- Retinopathy of Prematurity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
A single dosage of: 0.625mg(0.025cc)or 0.75mg(0.03cc) will be given intravitreally.
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab (Avastin) 0.75mg/0.03cc | Active comparator | 1/3 of study participants will be randomized to this treatment in one eye (study eye) and the other eye will receive laser (fellow eye) Receives: Drug: Bevacizumab |
| Bevacizumab (Avastin) 0.625mg/0.025cc | Active comparator | 1/3 of patients will be randomized to this treatment in 1 eye (study eye) and the other eye will receive laser (fellow eye). Receives: Drug: Bevacizumab |
| Laser ablation | Active comparator | 1/3 of study participants will be randomized to this treatment in both eyes (study eye and fellow eye) Receives: Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
To demonstrate non-inferiority of Anti-VEGF treatment to standard-of-care laser
It is the intent of this clinical study to develop alternative therapy (a single bevacizumab injection) to standard therapy (laser ablation) and to show that bevacizumab is as safe and efficacious as laser.
Measured: With patient #58, 116 and 174 (within 3 months after each patient being enrolled)
Secondary outcomes (1)
Decreased laser ablation and improved vascular maturity
These 2 end-points will be monitored by evidence of persistent disease and presence/absence of progression to retinal detachment. If either or both of these objectives are not met, it is indicative of failure of treatment.
Measured: With patient #58, 116 & 174 (within 3 months after each patient being enrolled)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2010 (estimated)
- Study startJun 2012
- Primary completionApr 2015 (estimated)
- Study completionJul 2018 (estimated)
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Retinopathy of PrematurityStudies 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vision Research Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael T. Trese, M.D., Vision Research Foundation
- Investigators
- Michael T Trese, MD, Principal investigator, Vision Research Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01232777
- Sponsor's protocol ID
- 002
- Acronym
- BLOCK-ROP
- Status last verified
- Oct 2013
- First submitted
- 26 Oct 2010
- Last updated
- 17 Oct 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity (BLOCK-ROP)
- ClinicalTrials.gov ID
- NCT01232777
- Acronym / sponsor ID
- BLOCK-ROP / 002
- Conditions
- Retinopathy of Prematurity
- Keywords
- Retinopathy of Prematurity, Bevacizumab, Avastin, Vascular Endothelial Growth Factor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Vision Research FoundationUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- Apr 2015 (estimated)
- Study completion
- Jul 2018 (estimated)
- First posted
- 2 Nov 2010 (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.
The purpose of this study is to determine whether a single intravitreal (into the gel of the eye) injection of Avastin 0.625mg or 0.75mg is equivalent (non-inferior) to treatment with standard of care laser in infants with Type I pre-threshold retinopathy of prematurity (ROP) diagnosed at 30-36 weeks gestational age.
Detailed description
Retinopathy of Prematurity (ROP) is a leading cause of blindness in children in developed countries around the world, and an increasing cause of blindness in developing countries.
The retina lines the inside of the eye. It functions as "film" within the camera, which is the eye. When an infant is born prematurely, the vascular network necessary to nourish the retina has not fully developed. As a consequence, in some infants abnormal vessels grow instead of the normal ones--a condition known as ROP. The abnormal vessels carry scar tissue along with them, and may lead to retinal detachment and blindness if the eye is not treated.
The multi-center trial of Cryotherapy for Retinopathy of Prematurity (CRYo-ROP) Study demonstrated that ablation of the peripheral avascular retina reduced the risk of poor structural and visual outcome due to retinal distortion or detachment in ROP (1980's). The ablated retina is not functional and is not amendable to regeneration.
Peripheral retinal ablation is not universally effective in fostering regression of ROP. This is particularly true for an aggressive form of ROP (aggressive posterior ROP, or APROP), which typically afflicts profoundly premature and sick neonates. In this subset of infants, progression of ROP to retinal detachments in both eyes and even blindness may occur despite timely and complete peripheral retinal laser ablation.
RATIONALE:
The development of ROP is largely dependant on vascular endothelial growth factor (VEGF). When an infant is born prematurely, the relatively hyperoxic environment that the baby is introduced to shuts down the production of VEGF. Retinal maturation is thus delayed. Subsequently, at a time when intraocular VEGF levels would be declining late in the third trimester of pregnancy, abnormally high levels of VEGF are seen due to large areas of avascular retina and associated tissue hypoxia.
The availability of FDA-approved drugs for anti-VEGF treatment renders it possible to treat such eye off-label. Available drugs include pegaptanib sodium (Macugen) for partial blockage of VEGF-A, or drugs such a ranibizumab (Lucentis) and bevacizumab (Avastin), which cause complete blockage of VEGF-A.
As VEGF is required in the developing retina for normal angiogenesis, and our goal is not to penetrate tissue, but to block the excessive levels of VEGF trapped within the overlying vitreous which is responsible for the abnormal vasculature in ROP.
For purposes of this study, we have chosen bevacizumab (Avastin) which will: a) attain complete blockage (vs. Macugen) of intravitreal VEGF-A, and b)which is limited in its ability to penetrate tissues because it is a full antibody (vs. Lucentis, an antibody fragment specifically designed for better tissue penetration), and is more likely to restore VEGF homeostasis within the developing retina.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab (Avastin) 0.75mg/0.03cc | Active comparator | Drug: Bevacizumab1/3 of study participants will be randomized to this treatment in one eye (study eye) and the other eye will receive laser (fellow eye) |
| Bevacizumab (Avastin) 0.625mg/0.025cc | Active comparator | Drug: Bevacizumab1/3 of patients will be randomized to this treatment in 1 eye (study eye) and the other eye will receive laser (fellow eye). |
| Laser ablation | Active comparator | Drug: Bevacizumab1/3 of study participants will be randomized to this treatment in both eyes (study eye and fellow eye) |
Who may qualify
- Ages
- 30 to 36 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Inborn babies at participating NICU's who meet inclusion criteria
- Outborn babies transferred to participating NICU's who meet inclusion criteria
- Type 1 pre-threshold ROP
- No prior treatment
- Post menstrual age less than 36 1/7 weeks
Key exclusion criteria (8 listed)
- Fatal systemic anomaly
- An ocular anomaly of one or both eye affecting the retina or choroid
- An ocular anomaly precluding use of the RetCam (ex., microphthalmia)
- Neonatologist feels inclusion will unduly challenge the infant
- Refusal of initial consent
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 |
|---|---|---|
| BevacizumabAlso: AvastinA single dosage of: 0.625mg(0.025cc)or 0.75mg(0.03cc) will be given intravitreally. | Drug | Bevacizumab (Avastin) 0.625mg/0.025cc, Bevacizumab (Avastin) 0.75mg/0.03cc, Laser ablation |
Primary outcome
To demonstrate non-inferiority of Anti-VEGF treatment to standard-of-care laser
Time frame: With patient #58, 116 and 174 (within 3 months after each patient being enrolled)
It is the intent of this clinical study to develop alternative therapy (a single bevacizumab injection) to standard therapy (laser ablation) and to show that bevacizumab is as safe and efficacious as laser.
1 secondary outcome
Decreased laser ablation and improved vascular maturity
Time frame: With patient #58, 116 & 174 (within 3 months after each patient being enrolled)
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 17 Oct 2013.
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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.
Michael T Trese, MD principal investigator
Vision Research Foundation
19 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab in people with Retinopathy of Prematurity, run by Vision Research Foundation at 19 sites in 2 countries.
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: withdrawn, as of the sponsor's last update on 17 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, Canada. 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 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?
To demonstrate non-inferiority of Anti-VEGF treatment to standard-of-care laser (time frame: With patient #58, 116 and 174 (within 3 months after each patient being enrolled)). 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 17 Oct 2013.