Retinopathy of PrematurityPhase 2BEAT-ROPNCT00622726
Bevacizumab Eliminates the Angiogenic Threat for Retinopathy of Prematurity
A Phase 2 study testing Bevacizumab and Conventional Laser for ROP in people with Retinopathy of Prematurity, run by The University of Texas Health Science Center, Houston at 15 sites in United States.
Trial summary
The purpose of this study was to determine the efficacy and additional advantages of intravitreal bevacizumab in the treatment of ROP for both Zone I and Zone II Posterior. Read more about this study
- Who is it for?
- Ages 4 to 22 weeks
- Conditions the study is for
- Retinopathy of Prematurity
- What is being tested?
- Bevacizumab and Conventional Laser for ROP
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 15 sitesUnited States
- Study dates
- Mar 2008to Aug 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 4 to 22 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants who have been screened by the American Academy of Ophthalmology, the American Academy of Pediatrics, and the American Association for Pediatric Ophthalmology and Strabismus guidelines (≤1500 grams at birth and ≤30 weeks gestation) who develop Stage 3 ROP in zone I or posterior zone II.
- Informed Consent from a parent or guardian.
Who cannot join
- Infants who have a congenital systemic anomaly or have a congenital ocular abnormality.
- Infants who cannot be treated by conventional laser therapy because of problems with media clarity. Generally, blind external cryotherapy would be utilized as an initial therapy and the infant would be excluded from the study even if the media clear subsequently.
- Informed Consent from a parent or guardian refused. This will mean that an infant automatically will receive laser therapy. Bevacizumab (Avastin®) treatment cannot be given outside of the Protocol. No data will be used from an infant without Informed Consent.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Palmetto Health Richland Hospital
Columbia, South Carolina, 29203
Palmetto Health Baptist Hospital
Columbia, South Carolina, 29223
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
Baylor University Medical Center
Dallas, Texas, 75346
Presbyterian-St. Luke's Hospital
Denver, Colorado, 80218
Las Palmas Medical Center
El Paso, Texas, 79902
R.E. Thomason Hospital
El Paso, Texas, 79905
Del Sol Medical Center
El Paso, Texas, 79925
Cook Children's Medical Center
Fort Worth, Texas, 76104
St. Joseph Medical Center
Houston, Texas, 77002
Children's Memorial Hermann Hospital
Houston, Texas, 77030
Memorial Hermann Southwest Hospital
Houston, Texas, 77074
Huntington Memorial Hospital
Pasadena, California, 91109
OSF St. Francis Medical Center-Children's Hospital of Illinois
Peoria, Illinois, 61637
Clear Lake Regional Medical Center
Webster, Texas, 77598
About this study
Official title: Intravitreal Bevacizumab (AvastinTM) Injections Versus Conventional Laser Surgery for Vision-threatening Retinopathy of Prematurity: a Prospective, Randomized, Non-blinded, Controlled, Multi-center, Clinical Trial
The purpose of this study was to determine the efficacy and additional advantages of intravitreal bevacizumab in the treatment of ROP for both Zone I and Zone II Posterior.
Read the detailed description
This phase 2 study assessed the anti-neovascularization activity of intravitreal bevacizumab, as determined by regression of neovascular vessels of retinopathy of prematurity (ROP), in neonates with acute stage 3 ROP in zone I or posterior zone II with plus disease. This study enrolled 150 confirmed cases of vision threatening ROP which have definite plus disease [ranging from Early Treatment for Retinopathy of Prematurity, to Cryotherapy for Retinopathy of Prematurity . This was done because of the controversy regarding determining plus disease and the increasing concern that many infants are being treated whose ROP would spontaneously regress. Bevacizumab will be administered intravitreally using 0.625 mg (0.025 ml) injections into each eye. There was no intent to give additional doses unless there was a recurrence of vision threatening stage 3 ROP with plus disease since the disease is self limited by completion of vascularization. Clinical response and any evidence of ocular toxicities were documented by retinal imaging system (manufactured by Clarity Medical Systems, Inc.) taken pre-injection, one week and one month post injection, and at 6 months of age (54 weeks postmenstrual age)(window of 50 to 70 weeks PMA)(primary outcome) and at 12 months of age (80 weeks postmenstrual age)(window of 75 to 100 weeks PMA)(structural documentation). Using the same retinal imaging system, fluorescein angiograms have been taken when possible to document structural outcomes in greater detail. No evidence of systemic toxicities were documented by appropriate clinical and laboratory tests.
- Conditions
- Retinopathy of Prematurity
- Being tested
- Bevacizumab, Conventional Laser for ROP
- Keywords
- Vascular Endothelial Growth Factor, Angiogenesis Inhibitor, Premature infants, Bevacizumab, Zone I or Posterior Zone II ROP, Aggressive Posterior ROP, Stage 3 ROP, Neonatal Intensive Care Unit
- Medical subject headings
- Retinopathy of Prematurity, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin; Monoclonal antibody
Anti-angiogenic drug: intravitreal injection of 0.625 mg (0.025 ml) once into each eye.
Conventional Laser for ROPProcedure or surgery
Also called Diode Laser is the laser utilized for this study
Conventional Laser is applied to the Avascular Peripheral Retina (Anterior to the Vascularized Posterior Retina)
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab for ROP | Experimental | Intravitreal Bevacizumab Therapy is the Experimental Arm of this Study Receives: Drug: Bevacizumab |
| Conventional Laser for ROP | Active comparator | Conventional Laser to the Peripheral Retina is the Control Arm of this Study Receives: Procedure: Conventional Laser for ROP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Eyes Showing Recurrence of Neovascularization Arising From the Retinal Vessels and Requiring Re-treatment
For Bevacizumab: Regrowth of new vessels at the site of the original extraretinal fibrovascular proliferation and/or at the site of the anterior edge of inner retinal vascularization.
For Laser: Regrowth of new vessels from the vessels at the anterior edge of inner retinal vascularization (remaining after retinal ablation).
Measured: 54 weeks postmenstrual age (window of 50 to 70 weeks)
Secondary outcomes (2)
Myopia in Zone I and Posterior Zone II of Infant Eyes
Myopia was determined via refraction using a retinoscope and lenses. Myopia is defined as a refractive error reported in Diopters.
Measured: 2.5 years of age
Visual Acuity
The visual acuity will be measured at 20 feet with figures or letters from all infants able to cooperate.
Measured: Age 7 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2008 (estimated)
- Study startMar 2008
- Primary completionAug 2010
- Study completionAug 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Retinopathy of PrematurityStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Helen Mintz-Hittner, MD, The University of Texas Health Science Center, Houston
- Investigators
- Helen A. Mintz-Hittner, M.D., Principal investigator, The University of Texas Health Science Center, Houston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00622726
- Sponsor's protocol ID
- HSC-MS-08-0036
- Other IDs
- IND: 101,578
- Acronym
- BEAT-ROP
- Status last verified
- May 2017
- First submitted
- 13 Feb 2008
- Last updated
- 6 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Mintz-Hittner HA, Best LM. Antivascular endothelial growth factor for retinopathy of prematurity. Curr Opin Pediatr. 2009 Apr;21(2):182-7. doi: 10.1097/MOP.0b013e32832925f9.
PubMed 19300261Mintz-Hittner HA. Avastin as monotherapy for retinopathy of prematurity. J AAPOS. 2010 Feb;14(1):2-3. doi: 10.1016/j.jaapos.2009.12.002. No abstract available.
PubMed 20227612Mintz-Hittner HA. Intravitreal pegaptanib as adjunctive treatment for stage 3+ ROP shown to be effective in a prospective, randomized, controlled multicenter clinical trial. Eur J Ophthalmol. 2012 Sep-Oct;22(5):685-6. doi: 10.5301/ejo.5000176.
PubMed 22669847Mintz-Hittner HA. Treatment of retinopathy of prematurity with vascular endothelial growth factor inhibitors. Early Hum Dev. 2012 Dec;88(12):937-41. doi: 10.1016/j.earlhumdev.2012.09.019. Epub 2012 Oct 15.
PubMed 23078830Mintz-Hittner HA, Kuffel RR Jr. Intravitreal injection of bevacizumab (avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II. Retina. 2008 Jun;28(6):831-8. doi: 10.1097/IAE.0b013e318177f934.
PubMed 18536599Kong L, Mintz-Hittner HA, Penland RL, Kretzer FL, Chevez-Barrios P. Intravitreous bevacizumab as anti-vascular endothelial growth factor therapy for retinopathy of prematurity: a morphologic study. Arch Ophthalmol. 2008 Aug;126(8):1161-3. doi: 10.1001/archophthalmol.2008.1. No abstract available.
PubMed 18695118Mintz-Hittner HA, Kennedy KA, Chuang AZ; BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011 Feb 17;364(7):603-15. doi: 10.1056/NEJMoa1007374.
PubMed 21323540Geloneck MM, Chuang AZ, Clark WL, Hunt MG, Norman AA, Packwood EA, Tawansy KA, Mintz-Hittner HA; BEAT-ROP Cooperative Group. Refractive outcomes following bevacizumab monotherapy compared with conventional laser treatment: a randomized clinical trial. JAMA Ophthalmol. 2014 Nov;132(11):1327-33. doi: 10.1001/jamaophthalmol.2014.2772.
PubMed 25103848Mintz-Hittner HA, Geloneck MM, Chuang AZ. Clinical Management of Recurrent Retinopathy of Prematurity after Intravitreal Bevacizumab Monotherapy. Ophthalmology. 2016 Sep;123(9):1845-55. doi: 10.1016/j.ophtha.2016.04.028. Epub 2016 May 27.
PubMed 27241619
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravitreal Bevacizumab (AvastinTM) Injections Versus Conventional Laser Surgery for Vision-threatening Retinopathy of Prematurity: a Prospective, Randomized, Non-blinded, Controlled, Multi-center, Clinical Trial
- ClinicalTrials.gov ID
- NCT00622726
- Acronym / sponsor ID
- BEAT-ROP / HSC-MS-08-0036
- Conditions
- Retinopathy of Prematurity
- Keywords
- Vascular Endothelial Growth Factor, Angiogenesis Inhibitor, Premature infants, Bevacizumab, Zone I or Posterior Zone II ROP, Aggressive Posterior ROP, Stage 3 ROP, Neonatal Intensive Care Unit
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Study start
- Mar 2008 (actual)
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2020 (estimated)
- First posted
- 25 Feb 2008 (estimated)
- Results
- Posted 9 Jun 2014
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 was to determine the efficacy and additional advantages of intravitreal bevacizumab in the treatment of ROP for both Zone I and Zone II Posterior.
Detailed description
This phase 2 study assessed the anti-neovascularization activity of intravitreal bevacizumab, as determined by regression of neovascular vessels of retinopathy of prematurity (ROP), in neonates with acute stage 3 ROP in zone I or posterior zone II with plus disease. This study enrolled 150 confirmed cases of vision threatening ROP which have definite plus disease [ranging from Early Treatment for Retinopathy of Prematurity, to Cryotherapy for Retinopathy of Prematurity . This was done because of the controversy regarding determining plus disease and the increasing concern that many infants are being treated whose ROP would spontaneously regress. Bevacizumab will be administered intravitreally using 0.625 mg (0.025 ml) injections into each eye. There was no intent to give additional doses unless there was a recurrence of vision threatening stage 3 ROP with plus disease since the disease is self limited by completion of vascularization. Clinical response and any evidence of ocular toxicities were documented by retinal imaging system (manufactured by Clarity Medical Systems, Inc.) taken pre-injection, one week and one month post injection, and at 6 months of age (54 weeks postmenstrual age)(window of 50 to 70 weeks PMA)(primary outcome) and at 12 months of age (80 weeks postmenstrual age)(window of 75 to 100 weeks PMA)(structural documentation). Using the same retinal imaging system, fluorescein angiograms have been taken when possible to document structural outcomes in greater detail. No evidence of systemic toxicities were documented by appropriate clinical and laboratory tests.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab for ROP | Experimental | Drug: BevacizumabIntravitreal Bevacizumab Therapy is the Experimental Arm of this Study |
| Conventional Laser for ROP | Active comparator | Procedure: Conventional Laser for ROPConventional Laser to the Peripheral Retina is the Control Arm of this Study |
Who may qualify
- Ages
- 4 to 22 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Infants who have been screened by the American Academy of Ophthalmology, the American Academy of Pediatrics, and the American Association for Pediatric Ophthalmology and Strabismus guidelines (≤1500 grams at birth and ≤30 weeks gestation) who develop Stage 3 ROP in zone I or posterior zone II.
- Informed Consent from a parent or guardian.
Key exclusion criteria (3 listed)
- Infants who have a congenital systemic anomaly or have a congenital ocular abnormality.
- Infants who cannot be treated by conventional laser therapy because of problems with media clarity. Generally, blind external cryotherapy would be utilized as an initial therapy and the infant would be excluded from the study even if the media clear subsequently.
- Informed Consent from a parent or guardian refused. This will mean that an infant automatically will receive laser therapy. Bevacizumab (Avastin®) treatment cannot be given outside of the Protocol. No data will be used from an infant without Informed 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: Avastin; Monoclonal antibodyAnti-angiogenic drug: intravitreal injection of 0.625 mg (0.025 ml) once into each eye. | Drug | Bevacizumab for ROP |
| Conventional Laser for ROPAlso: Diode Laser is the laser utilized for this studyConventional Laser is applied to the Avascular Peripheral Retina (Anterior to the Vascularized Posterior Retina) | Procedure or surgery | Conventional Laser for ROP |
Primary outcome
Number of Eyes Showing Recurrence of Neovascularization Arising From the Retinal Vessels and Requiring Re-treatment
Time frame: 54 weeks postmenstrual age (window of 50 to 70 weeks)
For Bevacizumab: Regrowth of new vessels at the site of the original extraretinal fibrovascular proliferation and/or at the site of the anterior edge of inner retinal vascularization. For Laser: Regrowth of new vessels from the vessels at the anterior edge of inner retinal vascularization (remaining after retinal ablation).
2 secondary outcomes
Myopia in Zone I and Posterior Zone II of Infant Eyes
Time frame: 2.5 years of age
Visual Acuity
Time frame: Age 7 years.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19300261Mintz-Hittner HA, Best LM. Antivascular endothelial growth factor for retinopathy of prematurity. Curr Opin Pediatr. 2009 Apr;21(2):182-7. doi: 10.1097/MOP.0b013e32832925f9.
- Background: PubMed 20227612Mintz-Hittner HA. Avastin as monotherapy for retinopathy of prematurity. J AAPOS. 2010 Feb;14(1):2-3. doi: 10.1016/j.jaapos.2009.12.002. No abstract available.
- Background: PubMed 22669847Mintz-Hittner HA. Intravitreal pegaptanib as adjunctive treatment for stage 3+ ROP shown to be effective in a prospective, randomized, controlled multicenter clinical trial. Eur J Ophthalmol. 2012 Sep-Oct;22(5):685-6. doi: 10.5301/ejo.5000176.
- Background: PubMed 23078830Mintz-Hittner HA. Treatment of retinopathy of prematurity with vascular endothelial growth factor inhibitors. Early Hum Dev. 2012 Dec;88(12):937-41. doi: 10.1016/j.earlhumdev.2012.09.019. Epub 2012 Oct 15.
- Results publication: PubMed 18536599Mintz-Hittner HA, Kuffel RR Jr. Intravitreal injection of bevacizumab (avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II. Retina. 2008 Jun;28(6):831-8. doi: 10.1097/IAE.0b013e318177f934.
- Results publication: PubMed 18695118Kong L, Mintz-Hittner HA, Penland RL, Kretzer FL, Chevez-Barrios P. Intravitreous bevacizumab as anti-vascular endothelial growth factor therapy for retinopathy of prematurity: a morphologic study. Arch Ophthalmol. 2008 Aug;126(8):1161-3. doi: 10.1001/archophthalmol.2008.1. No abstract available.
- Results publication: PubMed 21323540Mintz-Hittner HA, Kennedy KA, Chuang AZ; BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011 Feb 17;364(7):603-15. doi: 10.1056/NEJMoa1007374.
- Results publication: PubMed 25103848Geloneck MM, Chuang AZ, Clark WL, Hunt MG, Norman AA, Packwood EA, Tawansy KA, Mintz-Hittner HA; BEAT-ROP Cooperative Group. Refractive outcomes following bevacizumab monotherapy compared with conventional laser treatment: a randomized clinical trial. JAMA Ophthalmol. 2014 Nov;132(11):1327-33. doi: 10.1001/jamaophthalmol.2014.2772.
- Results publication: PubMed 27241619Mintz-Hittner HA, Geloneck MM, Chuang AZ. Clinical Management of Recurrent Retinopathy of Prematurity after Intravitreal Bevacizumab Monotherapy. Ophthalmology. 2016 Sep;123(9):1845-55. doi: 10.1016/j.ophtha.2016.04.028. Epub 2016 May 27.
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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.
Helen A. Mintz-Hittner, M.D. principal investigator
The University of Texas Health Science Center, Houston
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab and Conventional Laser for ROP in people with Retinopathy of Prematurity, run by The University of Texas Health Science Center, Houston at 15 sites 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 2 inclusion and 3 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 6 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites 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. 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?
Yes. Results are posted in the registry (first posted 9 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Eyes Showing Recurrence of Neovascularization Arising From the Retinal Vessels and Requiring Re-treatment (time frame: 54 weeks postmenstrual age (window of 50 to 70 weeks)). 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 NCT00622726, which also lists 9 linked publications.
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 6 Jun 2017.