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Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity (CARE-ROP)

Primary Purpose

Retinopathy of Prematurity (ROP)

Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
ranibizumab
Sponsored by
University Hospital Freiburg
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Retinopathy of Prematurity (ROP)

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Bilateral ROP in zone I (stage 1+, 2+, 3+/-, AP-ROP) or ROP in central (=posterior) zone II (stage 3+, AP-ROP). Zone I is defined as twice the distance from the optic disc to the fovea measured temporally, posterior zone II is defined as three times the distance from the optic disc to the fovea measured temporally.
  • Legal representatives or their designates willing and able to attend regular study visits with the study infant.
  • Written informed consent to participate in the study (signed by all patient's legal representatives).

Exclusion Criteria:

  • Pediatric conditions rendering the infant ineligible to anti-VEGF treatment or to repeated blood draws as evaluated by a neonatal ICU specialist and a study ophthalmologist.
  • Congenital brain lesions significantly impairing optic nerve function.
  • Severe hydrocephalus with significantly increased intracranial pressure.
  • Advanced stages of ROP with partial or complete retinal detachment (ROP stage 4 and 5).
  • ROP involving only the peripheral retina (i.e. peripheral zone II or zone III).
  • Known hypersensitivity to the study drug or to drugs with similar chemical structures.
  • Contraindications for an intravitreal injection as listed in ranibizumab SmPC.
  • Systemic use of anti-VEGF therapeutics.
  • Use of other investigational drugs - excluding vitamins and minerals - at the time of enrollment, or within 30 days or 5 half-lives prior to enrollment, whichever is longer.

Sites / Locations

  • University Eye Hospital
  • University Eye Hospital
  • University Eye Hospital
  • University Eye Hospital
  • University Eye Hospital
  • University Eye Hospital
  • University Eye Hospital
  • University Eye Hospital
  • University Eye Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Ranibizumab 0.12 mg

Ranibizumab 0.20 mg

Arm Description

20 µl of the 6 mg/ml ranibizumab concentration will be applied intravitreally. After an initial response the same dose as in the first injection can be re-applied after at least four weeks post injection. A maximum number of 3 regular re-injections can be applied.

20 µl of the 10 mg/ml ranibizumab concentration will be applied intravitreally. After an initial response the same dose as in the first injection can be re-applied after at least four weeks post injection. A maximum number of 3 re-injections can be applied.

Outcomes

Primary Outcome Measures

Efficacy of treatment
Efficacy is determined by the number of infants without need for rescue treatment up to week 24 post first injection. Re-injection of study dose is not considered rescue treatment if applied after an initial response to treatment and after at least 4 weeks post injection.

Secondary Outcome Measures

Regression of plus disease
Regression of preretinal vascularized ridge
Progression of peripheral intraretinal vascularization beyond ridge
Number and kind of AEs and SAEs
Changes in vascular endothelial growth factor (VEGF) levels in the systemic circulation
Number of re-injections of study dose
Number of patients progressing to stage 4 or 5 ROP
Number of patients with complete vascularization of the peripheral retina to within one disc diameter of the ora serrata

Full Information

First Posted
April 26, 2014
Last Updated
March 8, 2017
Sponsor
University Hospital Freiburg
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1. Study Identification

Unique Protocol Identification Number
NCT02134457
Brief Title
Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity
Acronym
CARE-ROP
Official Title
Multicenter Randomized Double Masked Parallel Design Exploratory Study to Assess Safety and Efficacy of Two Different Doses of Intravitreal Anti-VEGF Treatment With Ranibizumab (0.12 mg vs. 0.20 mg) in Infants With Retinopathy of Prematurity (ROP)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Freiburg

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is designed as an exploratory study to assess safety and efficacy of two different doses of the anti-VEGF agent ranibizumab (0.12 mg vs. 0.20 mg) in the treatment of infants with retinopathy of prematurity. Furthermore it shall help to improve safety in the treatment of ROP and provide explorative data on long-term effects of ranibizumab after intravitreal injection in neonates. The primary objective is to assess clinical efficacy of ranibizumab in children with ROP

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retinopathy of Prematurity (ROP)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ranibizumab 0.12 mg
Arm Type
Experimental
Arm Description
20 µl of the 6 mg/ml ranibizumab concentration will be applied intravitreally. After an initial response the same dose as in the first injection can be re-applied after at least four weeks post injection. A maximum number of 3 regular re-injections can be applied.
Arm Title
Ranibizumab 0.20 mg
Arm Type
Experimental
Arm Description
20 µl of the 10 mg/ml ranibizumab concentration will be applied intravitreally. After an initial response the same dose as in the first injection can be re-applied after at least four weeks post injection. A maximum number of 3 re-injections can be applied.
Intervention Type
Biological
Intervention Name(s)
ranibizumab
Other Intervention Name(s)
Lucentis
Primary Outcome Measure Information:
Title
Efficacy of treatment
Description
Efficacy is determined by the number of infants without need for rescue treatment up to week 24 post first injection. Re-injection of study dose is not considered rescue treatment if applied after an initial response to treatment and after at least 4 weeks post injection.
Time Frame
Up to 24 weeks post first injection
Secondary Outcome Measure Information:
Title
Regression of plus disease
Time Frame
Up to 24 weeks post first injection
Title
Regression of preretinal vascularized ridge
Time Frame
Up to 24 weeks post first injection
Title
Progression of peripheral intraretinal vascularization beyond ridge
Time Frame
Up to 24 weeks post first injection
Title
Number and kind of AEs and SAEs
Time Frame
Up to 24 weeks post first injection
Title
Changes in vascular endothelial growth factor (VEGF) levels in the systemic circulation
Time Frame
Up to 24 weeks post first injection
Title
Number of re-injections of study dose
Time Frame
Up to 24 weeks post first injection
Title
Number of patients progressing to stage 4 or 5 ROP
Time Frame
Up to 24 weeks post first injection
Title
Number of patients with complete vascularization of the peripheral retina to within one disc diameter of the ora serrata
Time Frame
Up to 24 weeks post first injection
Other Pre-specified Outcome Measures:
Title
Number of late recurrences of ROP during the follow-up period
Time Frame
Up to 5 years post first injection
Title
Number of patients progressing to stage 4 or 5 ROP after the core study
Time Frame
Up to 5 years post first injection
Title
Number of patients with complete vascularization of the peripheral retina to within one disc diameter of the ora serrata after the end of the core study
Time Frame
Up to 5 years post first injection
Title
Long-term ophthalmological development: visual acuity (if possible), orthoptic status, cycloplegic retinoscopy, refraction, IOP, fundoscopy including fundus photographs
Description
At one year and at 5 years an ophthalmological visit will take place.
Time Frame
Up to 5 years post first injection
Title
Long-term pediatric development: Bayley-test, weight, height, cognitive, motor and sensory development
Time Frame
Up to 5 years post first injection
Title
Number and kind of AEs or SAEs per group between the end of the observational core study and the end of the follow-up period
Time Frame
Up to 5 years post first injection

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Bilateral ROP in zone I (stage 1+, 2+, 3+/-, AP-ROP) or ROP in central (=posterior) zone II (stage 3+, AP-ROP). Zone I is defined as twice the distance from the optic disc to the fovea measured temporally, posterior zone II is defined as three times the distance from the optic disc to the fovea measured temporally. Legal representatives or their designates willing and able to attend regular study visits with the study infant. Written informed consent to participate in the study (signed by all patient's legal representatives). Exclusion Criteria: Pediatric conditions rendering the infant ineligible to anti-VEGF treatment or to repeated blood draws as evaluated by a neonatal ICU specialist and a study ophthalmologist. Congenital brain lesions significantly impairing optic nerve function. Severe hydrocephalus with significantly increased intracranial pressure. Advanced stages of ROP with partial or complete retinal detachment (ROP stage 4 and 5). ROP involving only the peripheral retina (i.e. peripheral zone II or zone III). Known hypersensitivity to the study drug or to drugs with similar chemical structures. Contraindications for an intravitreal injection as listed in ranibizumab SmPC. Systemic use of anti-VEGF therapeutics. Use of other investigational drugs - excluding vitamins and minerals - at the time of enrollment, or within 30 days or 5 half-lives prior to enrollment, whichever is longer.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas Stahl, MD
Organizational Affiliation
University Eye Hospital Freiburg, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Eye Hospital
City
Freiburg
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
79106
Country
Germany
Facility Name
University Eye Hospital
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
University Eye Hospital
City
Duesseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
University Eye Hospital
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
University Eye Hospital
City
Magdeburg
ZIP/Postal Code
39120
Country
Germany
Facility Name
University Eye Hospital
City
Muenster
ZIP/Postal Code
48149
Country
Germany
Facility Name
University Eye Hospital
City
Munich
ZIP/Postal Code
80336
Country
Germany
Facility Name
University Eye Hospital
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
University Eye Hospital
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
29309486
Citation
Stahl A, Krohne TU, Eter N, Oberacher-Velten I, Guthoff R, Meltendorf S, Ehrt O, Aisenbrey S, Roider J, Gerding H, Jandeck C, Smith LEH, Walz JM; Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity (CARE-ROP) Study Group. Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity: A Randomized Clinical Trial. JAMA Pediatr. 2018 Mar 1;172(3):278-286. doi: 10.1001/jamapediatrics.2017.4838.
Results Reference
derived

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Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity

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