Retinopathy of Prematurity (ROP)Phase 2CARE-ROPNCT02134457
Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity
A Phase 2 study testing ranibizumab in people with Retinopathy of Prematurity (ROP), run by University Hospital Freiburg at 9 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Retinopathy of Prematurity (ROP)
- What is being tested?
- ranibizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 9 sitesGermany
- Study dates
- Aug 2014to Jan 2017
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Germany9 sites
University Eye Hospital
Bonn, 53127
University Eye Hospital
Düsseldorf, 40225
University Eye Hospital
Freiburg im Breisgau, Baden-Wurttemberg, 79106
University Eye Hospital
Kiel, 24105
University Eye Hospital
Magdeburg, 39120
University Eye Hospital
Munich, 80336
University Eye Hospital
Münster, 48149
University Eye Hospital
Regensburg, 93053
University Eye Hospital
Tübingen, 72076
About this study
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)
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
- Conditions
- Retinopathy of Prematurity (ROP)
- Being tested
- ranibizumab
- 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.
ranibizumabBiological
Also called Lucentis
| Study group | Role | What they receive |
|---|---|---|
| Ranibizumab 0.12 mg | Experimental | 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. Receives: Biological: ranibizumab |
| Ranibizumab 0.20 mg | Experimental | 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. Receives: Biological: ranibizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 24 weeks post first injection
Secondary outcomes (8)
Regression of plus disease
Measured: Up to 24 weeks post first injection
Regression of preretinal vascularized ridge
Measured: Up to 24 weeks post first injection
Progression of peripheral intraretinal vascularization beyond ridge
Measured: Up to 24 weeks post first injection
Number and kind of AEs and SAEs
Measured: Up to 24 weeks post first injection
Changes in vascular endothelial growth factor (VEGF) levels in the systemic circulation
Measured: Up to 24 weeks post first injection
Number of re-injections of study dose
Measured: Up to 24 weeks post first injection
Number of patients progressing to stage 4 or 5 ROP
Measured: Up to 24 weeks post first injection
Number of patients with complete vascularization of the peripheral retina to within one disc diameter of the ora serrata
Measured: Up to 24 weeks post first injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2014 (estimated)
- Study startAug 2014
- Primary completionJan 2017
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Retinopathy of Prematurity (ROP)Studies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Freiburg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andreas Stahl, MD, University Hospital Freiburg
- Investigators
- Andreas Stahl, MD, Principal investigator, University Eye Hospital Freiburg, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02134457
- Sponsor's protocol ID
- CARE-ROP
- Other IDs
- 2013-002539-13
- Acronym
- CARE-ROP
- Status last verified
- Mar 2017
- First submitted
- 26 Apr 2014
- Last updated
- 9 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 29309486
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02134457
- Acronym / sponsor ID
- CARE-ROP / CARE-ROP
- Conditions
- Retinopathy of Prematurity (ROP)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University Hospital FreiburgUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 9 May 2014 (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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ranibizumab 0.12 mg | Experimental | Biological: ranibizumab20 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. |
| Ranibizumab 0.20 mg | Experimental | Biological: ranibizumab20 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (9 listed)
- 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).
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 |
|---|---|---|
| ranibizumabAlso: Lucentis | Biological | Ranibizumab 0.12 mg, Ranibizumab 0.20 mg |
Primary outcome
Efficacy of treatment
Time frame: Up to 24 weeks post first injection
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.
8 secondary outcomes
Regression of plus disease
Time frame: Up to 24 weeks post first injection
Regression of preretinal vascularized ridge
Time frame: Up to 24 weeks post first injection
Progression of peripheral intraretinal vascularization beyond ridge
Time frame: Up to 24 weeks post first injection
Number and kind of AEs and SAEs
Time frame: Up to 24 weeks post first injection
Changes in vascular endothelial growth factor (VEGF) levels in the systemic circulation
Time frame: Up to 24 weeks post first injection
Number of re-injections of study dose
Time frame: Up to 24 weeks post first injection
Number of patients progressing to stage 4 or 5 ROP
Time frame: Up to 24 weeks post first injection
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2017.
- Derived from this study: PubMed 29309486Stahl 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.
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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.
Andreas Stahl, MD principal investigator
University Eye Hospital Freiburg, Germany
9 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 ranibizumab in people with Retinopathy of Prematurity (ROP), run by University Hospital Freiburg at 9 sites in Germany.
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 3 inclusion and 9 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: finished, as of the sponsor's last update on 9 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Germany. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Efficacy of treatment (time frame: Up to 24 weeks post first injection). 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 NCT02134457, which also lists 1 linked publication.
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 9 Mar 2017.