Bevacizumab Eliminates the Angiogenic Threat for Retinopathy of Prematurity

Retinopathy of Prematurity Clinical Trial

— BEAT-ROP  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00622726
• Other study ID #: HSC-MS-08-0036
• Secondary ID: IND: 101,578
• Status: Active, not recruiting
• Phase: Phase 2
• First received: February 13, 2008
• Last updated: July 6, 2015
• Start date: March 2008
• Est. completion date: October 2017

Study information

• Verified date: July 2015
• Source: The University of Texas Health Science Center, Houston
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: October 2017
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 22 Weeks

Eligibility

Inclusion Criteria:

1. 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.

2. Informed Consent from a parent or guardian.

Exclusion Criteria:

1. Infants who have a congenital systemic anomaly or have a congenital ocular abnormality.

2. 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.

3. 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Premature Birth
• Retinal Diseases
• Retinopathy of Prematurity

Intervention

Drug:
• Bevacizumab
Anti-angiogenic drug: intravitreal injection of 0.625 mg (0.025 ml) once into each eye.

Procedure:
• Conventional Laser for ROP
Conventional Laser is applied to the Avascular Peripheral Retina (Anterior to the Vascularized Posterior Retina)

Locations

Country	Name	City	State
United States	Palmetto Health Baptist Hospital	Columbia	South Carolina
United States	Palmetto Health Richland Hospital	Columbia	South Carolina
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Baylor University Medical Center	Dallas	Texas
United States	Presbyterian-St. Luke's Hospital	Denver	Colorado
United States	Del Sol Medical Center	El Paso	Texas
United States	Las Palmas Medical Center	El Paso	Texas
United States	R.E. Thomason Hospital	El Paso	Texas
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Children's Memorial Hermann Hospital	Houston	Texas
United States	Memorial Hermann Southwest Hospital	Houston	Texas
United States	St. Joseph Medical Center	Houston	Texas
United States	Huntington Memorial Hospital	Pasadena	California
United States	OSF St. Francis Medical Center-Children's Hospital of Illinois	Peoria	Illinois
United States	Clear Lake Regional Medical Center	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston

Country where clinical trial is conducted

United States, 

References & Publications (8)

Geloneck 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. JAM — View Citation

Kong L, Mintz-Hittner HA, Penland RL, Kretzer FL, Chévez-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/arc — View Citation

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. Review. — View Citation

Mintz-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. — View Citation

Mintz-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. Erratum in: Retina. 2008 O — View Citation

Mintz-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. — View Citation

Mintz-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. — View Citation

Mintz-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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	54 weeks postmenstrual age (window of 50 to 70 weeks)	No
Secondary	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.	2.5 years of age	No
Secondary	Visual Acuity	The visual acuity will be measured at 20 feet with figures or letters from all infants able to cooperate.	Age 7 years.	No