Bevacizumab Eliminates the Angiogenic Threat for Retinopathy of Prematurity

NCT ID: NCT00622726

Last Updated: 2017-06-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2020-08-31

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bevacizumab for ROP

Intravitreal Bevacizumab Therapy is the Experimental Arm of this Study

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

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

Conventional Laser for ROP

Conventional Laser to the Peripheral Retina is the Control Arm of this Study

Group Type: ACTIVE_COMPARATOR

Conventional Laser for ROP

Intervention Type: PROCEDURE

Conventional Laser is applied to the Avascular Peripheral Retina (Anterior to the Vascularized Posterior Retina)

Interventions

Bevacizumab

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

Intervention Type: DRUG

Conventional Laser for ROP

Conventional Laser is applied to the Avascular Peripheral Retina (Anterior to the Vascularized Posterior Retina)

Intervention Type: PROCEDURE

Other Intervention Names

Avastin; Monoclonal antibody; Diode Laser is the laser utilized for this study

Eligibility Criteria

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.

• Minimum Eligible Age: 4 Weeks
• Maximum Eligible Age: 22 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Helen Mintz-Hittner, MD

Clinical Professor - Pediatric Ophthalmology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Helen A. Mintz-Hittner, M.D.

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

Huntington Memorial Hospital

Pasadena, California, United States

Presbyterian-St. Luke's Hospital

Denver, Colorado, United States

OSF St. Francis Medical Center-Children's Hospital of Illinois

Peoria, Illinois, United States

Palmetto Health Richland Hospital

Columbia, South Carolina, United States

Palmetto Health Baptist Hospital

Columbia, South Carolina, United States

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Baylor University Medical Center

Dallas, Texas, United States

Las Palmas Medical Center

El Paso, Texas, United States

R.E. Thomason Hospital

El Paso, Texas, United States

Del Sol Medical Center

El Paso, Texas, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

St. Joseph Medical Center

Houston, Texas, United States

Children's Memorial Hermann Hospital

Houston, Texas, United States

Memorial Hermann Southwest Hospital

Houston, Texas, United States

Clear Lake Regional Medical Center

Webster, Texas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 19300261 (View on PubMed)

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. No abstract available.

Reference Type: BACKGROUND

PMID: 20227612 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22669847 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23078830 (View on PubMed)

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.

Reference Type: RESULT

PMID: 18536599 (View on PubMed)

Kong 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.

Reference Type: RESULT

PMID: 18695118 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21323540 (View on PubMed)

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. JAMA Ophthalmol. 2014 Nov;132(11):1327-33. doi: 10.1001/jamaophthalmol.2014.2772.

Reference Type: RESULT

PMID: 25103848 (View on PubMed)

Mintz-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.

Reference Type: RESULT

PMID: 27241619 (View on PubMed)

Other Identifiers

IND: 101,578

Identifier Type: OTHER

Identifier Source: secondary_id

HSC-MS-08-0036

Identifier Type: -

Identifier Source: org_study_id