Diabetic Macular EdemaDEVITRANCT04387604
Effect of the Vitreous in Response to Intravitreal Injections of Ranibizumab for the Treatment of Diabetic Macular Edema
An observational study of Diabetic Macular Edema, run by Centro Hospitalar do Porto at 1 site in Portugal.
Trial summary
PURPOSE: To evaluate the effect of the vitreous in response to intravitreal (IV) injections of ranibizumab 0.5 mg/0.05ml (Lucentis; Genentech, South San Francisco, CA) for the treatment of diabetic macular edema (DME). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Diabetic Macular Edema
- What is being tested?
- Ranibizumab 0.5 MG/0.05 ML Intraocular Solution [LUCENTIS]
- Type of treatment
- Injection or infusion
- How many people
- 50 participants
- Where
- 1 sitePortugal
- Study dates
- 1 Aug 2017to 1 Mar 2019
- Phase
- Observational
- 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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All patients with DME followed on the ocular diabetes consultation of Centro Hospitalar e Universitário do Porto, Portugal, or Hospital Santa Maria Maior de Barcelos, Portugal, either non vitrectomized or vitrectomized.
Who may be able to join
- at least 18 years of age with either type 1 or type 2 diabetes mellitus;
- maximal central subfield foveal thickness (CSF) of at least 300μm (according to SD-OCT images - Spectral Domain Optical Coherence Tomography);
- BCVA of 20 to 80 letters, using ETDRS letters chart;
- ability to provide written informed consent.
Who cannot join
- Pregnant or lactating;
- Epiretinal membrane (ERM) existence in the study eye;
- persistent posterior hyaloid adherence after vitrectomy for group 2;
- previous vitrectomy for group 1;
- history of other retinal vascular diseases in the study eye;
- LASER photocoagulation or intravitreal injections (IV) of anti-VEGF or systemic anti-VEGF or pro-anti-VEGF treatment and cataract surgery in the 6 months previously to the study eye inclusion;
Show all 19Show fewer
- IV or peribulbar corticosteroid injections in the 6 months previously to study eye inclusion;
- history of IV of implant of fluocinolone acetonide in the study eye;
- vitreous hemorrhage or opacification in the study eye;
- active proliferative diabetic retinopathy in the study eye;
- active ocular inflammation or infection in either eye;
- aphakia in the study eye;
- other causes for macular edema, for example, after cataract surgery in the study eye;
- other causes of visual loss in the study eye;
- other diseases that may affect the course of macular edema in the study eye;
- uncontrolled glaucoma in either eye (intraocular pressure > 24 mmHg with treatment);
- history of arterial thrombotic event in the previous 6 months;
- uncontrolled arterial hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure > 100 mmHg);
- ward of the state.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of the Vitreous in Response to Intravitreal (IV) Injections of Ranibizumab (0.5mg/0.05ml) for the Treatment of Diabetic Macular Edema
PURPOSE: To evaluate the effect of the vitreous in response to intravitreal (IV) injections of ranibizumab 0.5 mg/0.05ml (Lucentis; Genentech, South San Francisco, CA) for the treatment of diabetic macular edema (DME).
METHODS: Prospective, observational, multicenter study, conducted at Centro Hospitalar e Universitário do Porto, Portugal. Best-corrected visual acuity and central foveal thickness will be evaluated at baseline and every month until the end of follow-up. OCT biomarkers such as retinal layers thickness will also be analyzed.
A p value of 0.05 or less will be considered to be statistically significant. HYPOTHESIS: Vitrectomized patients will improve less than non-vitrectomized patients.
Read the detailed description
Patients will be included in two different groups according to the vitreous status: group 1 - non vitrectomized eyes; group 2 - vitrectomized eyes. Patients will be followed-up according to the standard of care and a final analysis of the results will be performed at 12+/-1 months of follow-up, which is the minimum follow-up period required for each patient. In group 1 the effect of VMA existence and PVD status will also be analyzed. The recruitment period will be of 6 months.
Treatment All patients will be treated with IV ranibizumab injections (0.5 mg/0.05ml) following a PRN regimen. The injections will be performed in the operating room following the standard intravitreal injections protocol. When required, adjunct treatment, with macular and/or peripheral LASER (rescue LASER), will be also admitted at or after 24 weeks if persistent DME not improving after at least 2 injections.
Treatment Schedule Repeat injections at every 4-week visit if eye "improves" or "worsens" (defined as ≥5 letter change from last injection or ≥10% CST change on OCT from last injection or CSF>300 μm at any timepoint).
Defer injections if either BCVA of 85 letters and OCT CSF "normal" (CSF≤300 μm and non-existent intra- or sub-retinal fluid); or OCT CSF "normal" (CSF≤300 μm) and stable BCVA (defined as < 5 letters change from last injection) after two consecutive injections during the first 24 weeks, or after one injection if the initial stability period has already been achieved (OCT CSF "normal" and stable BCVA).
Resume injections if BCVA or OCT worsens.
- Conditions
- Diabetic Macular Edema
- Being tested
- Ranibizumab 0.5 MG/0.05 ML Intraocular Solution [LUCENTIS]
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ranibizumab 0.5 MG/0.05 ML Intraocular Solution [LUCENTIS]Drug
PRN regimen. Treatment Schedule Repeat injections at every 4-week visit if eye "improves" or "worsens" (defined as ≥5 letter change from last injection or ≥10% CST change on OCT from last injection or CSF>300 μm at any timepoint).
Defer injections if either BCVA of 85 letters and OCT CSF "normal" (CSF≤300 μm and non-existent intra- or sub-retinal fluid); or OCT CSF "normal" (CSF≤300 μm) and stable BCVA (defined as < 5 letters change from last injection) after two consecutive injections during the first 24 weeks, or after one injection if the initial stability period has already been achieved (OCT CSF "normal" and stable BCVA).
Resume injections if BCVA or OCT worsens.
| Study group | Role | What they receive |
|---|---|---|
| non vitrectomized eyes | ranibizumab injections (0.5 mg/0.05ml) following a PRN regimen Receives: Drug: Ranibizumab 0.5 MG/0.05 ML Intraocular Solution [LUCENTIS] | |
| vitrectomized eyes | ranibizumab injections (0.5 mg/0.05ml) following a PRN regimen Receives: Drug: Ranibizumab 0.5 MG/0.05 ML Intraocular Solution [LUCENTIS] |
What is being measured
The primary outcome is the main question the study is designed to answer.
assess the number of IV injections needed to control DME between groups
DME control is defined as 1) BCVA of 85 letters and OCT CFT "normal" (CFT≤300 μm and non-existent intra- or sub-retinal fluid); or 2) OCT CFT "normal" (CFT≤300 μm) and stable BCVA (defined as <5 letters change from last injection) after two consecutive injections during the first 24 weeks, or after one injection if the initial stability period has already been achieved (OCT CFT "normal" and stable BCVA).
Measured: 18 months
Secondary outcomes (5)
compare the functional changes at the end of follow-up between groups
Functional change will be measured by the Early Treatment Diabetic Retinopathy Scale (ETDRS) which measures the best-corrected visual acuity with an ETDRS-like chart at 4 meters in number letters or at 1 meter when patients are unable to read any letters on the ETDRS chart at 4 meters. The ETDRS scale varies from 1 to 85 letters (85 letters correspond to a 20/20 in the Snellen scale).
The higher the value the better the outcome. A clinical significant functional improvement will be considered for a gain of ≥5 EDTRS letters.
Measured: 18 months
compare the anatomical changes at the end of follow-up between groups
Anatomical change will be measured by central foveal thickness (CFT), measured by Optical Coherence Tomography, automatically measured by the software in the central 1 mm. A CFT <240µm or >300 µm is considered pathological. A CFT between 240 and 300 µm is considered physiological. CFT has no defined minimum or maximum values.
Since patients with diabetic macular edema usually have CFT >300 µm the goal of treatment is to lower the CFT to values between 240 and 300 µm. A clinical significant anatomical improvement will be considered for a change in CFT≥10%.
Measured: 18 months
compare the percentage of type of responder during the follow-up period between groups
Type of responder is defined as follows:
- good responder: when beyond the 24th week of follow-up (maximum 7 injections) there was a complete anatomical response (CFT≤300μm) with an increase in BCVA ≥5 letters;
- non-responder: 13 injections and final CFT >400 um or ≤10% of CFT reduction and BCVA decrease (or BCVA gain <5 letters)
- incomplete responder: between good and non-responder criteria.
Measured: 18 months
access the percentage, in group 2, of focal VMA and PVD status and type of response
to access the percentage, in group 2, of focal VMA and PVD status, and if those changed during the follow-up period influenced the type of response
Measured: 18 months
assess retinal layers thickness as prognostic and pathophysiological biomarkers of DME treatment response
- to assess baseline retinal layers thickness correlation with final BCVA
- to assess the influence of the variation of retinal layers thickness (baseline versus final) on final BCVA
- to assess differences between groups according to the above points;
- to associate the type of responder and baseline and final retinal layers thickness.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2020
- Study start1 Aug 2017
- Primary completion1 Feb 2018
- Study completion1 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diabetic Macular EdemaStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centro Hospitalar do Porto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bernardete Pessoa MD, Centro Hospitalar do Porto
- Investigators
- Bernardete Pessoa, MD, Principal investigator, Centro Hospitalar do Porto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04387604
- Sponsor's protocol ID
- 2017080120190301
- Acronym
- DEVITRA
- Status last verified
- May 2020
- First submitted
- 10 May 2020
- Last updated
- 14 May 2020
- Results posted
- No
- Individual data sharing
- No
Publications
Pessoa B, Leite J, Ferreira A, Ramalhao J, Pocas J, Jose D, Coelho C, Figueira J, Meireles A, Beirao JM. Oct biomarkers for early prognosis in diabetic macular edema treatment with ranibizumab. Eur J Ophthalmol. 2024 Jul;34(4):1141-1148. doi: 10.1177/11206721231210753. Epub 2023 Nov 3.
PubMed 37919940Pessoa B, Leite J, Heitor J, Coelho J, Monteiro S, Coelho C, Figueira J, Meireles A, Melo-Beirao JN. Vitrectomized versus non-vitrectomized eyes in diabetic macular edema response to ranibizumab-retinal layers thickness as prognostic biomarkers. Sci Rep. 2021 Nov 29;11(1):23055. doi: 10.1038/s41598-021-02532-4.
PubMed 34845300Pessoa B, Marques JH, Leite J, Silva N, Jose D, Coelho C, Figueira J, Meireles A, Melo-Beirao JN. Choroidal Blood Flow After Intravitreal Ranibizumab in Vitrectomized and Non-Vitrectomized Eyes with Diabetic Macular Edema. Clin Ophthalmol. 2021 Oct 9;15:4081-4090. doi: 10.2147/OPTH.S325037. eCollection 2021.
PubMed 34675476
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of the Vitreous in Response to Intravitreal (IV) Injections of Ranibizumab (0.5mg/0.05ml) for the Treatment of Diabetic Macular Edema
- ClinicalTrials.gov ID
- NCT04387604
- Acronym / sponsor ID
- DEVITRA / 2017080120190301
- Conditions
- Diabetic Macular Edema
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Centro Hospitalar do PortoUniversity, hospital or other
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 1 Feb 2018 (actual)
- Study completion
- 1 Mar 2019 (actual)
- First posted
- 14 May 2020 (actual)
- 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.
PURPOSE: To evaluate the effect of the vitreous in response to intravitreal (IV) injections of ranibizumab 0.5 mg/0.05ml (Lucentis; Genentech, South San Francisco, CA) for the treatment of diabetic macular edema (DME).
METHODS: Prospective, observational, multicenter study, conducted at Centro Hospitalar e Universitário do Porto, Portugal. Best-corrected visual acuity and central foveal thickness will be evaluated at baseline and every month until the end of follow-up. OCT biomarkers such as retinal layers thickness will also be analyzed.
A p value of 0.05 or less will be considered to be statistically significant. HYPOTHESIS: Vitrectomized patients will improve less than non-vitrectomized patients.
Detailed description
Patients will be included in two different groups according to the vitreous status: group 1 - non vitrectomized eyes; group 2 - vitrectomized eyes. Patients will be followed-up according to the standard of care and a final analysis of the results will be performed at 12+/-1 months of follow-up, which is the minimum follow-up period required for each patient. In group 1 the effect of VMA existence and PVD status will also be analyzed. The recruitment period will be of 6 months.
Treatment All patients will be treated with IV ranibizumab injections (0.5 mg/0.05ml) following a PRN regimen. The injections will be performed in the operating room following the standard intravitreal injections protocol. When required, adjunct treatment, with macular and/or peripheral LASER (rescue LASER), will be also admitted at or after 24 weeks if persistent DME not improving after at least 2 injections.
Treatment Schedule Repeat injections at every 4-week visit if eye "improves" or "worsens" (defined as ≥5 letter change from last injection or ≥10% CST change on OCT from last injection or CSF>300 μm at any timepoint).
Defer injections if either BCVA of 85 letters and OCT CSF "normal" (CSF≤300 μm and non-existent intra- or sub-retinal fluid); or OCT CSF "normal" (CSF≤300 μm) and stable BCVA (defined as < 5 letters change from last injection) after two consecutive injections during the first 24 weeks, or after one injection if the initial stability period has already been achieved (OCT CSF "normal" and stable BCVA).
Resume injections if BCVA or OCT worsens.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| non vitrectomized eyes | – | Drug: Ranibizumab 0.5 MG/0.05 ML Intraocular Solution [LUCENTIS]ranibizumab injections (0.5 mg/0.05ml) following a PRN regimen |
| vitrectomized eyes | – | Drug: Ranibizumab 0.5 MG/0.05 ML Intraocular Solution [LUCENTIS]ranibizumab injections (0.5 mg/0.05ml) following a PRN regimen |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All patients with DME followed on the ocular diabetes consultation of Centro Hospitalar e Universitário do Porto, Portugal, or Hospital Santa Maria Maior de Barcelos, Portugal, either non vitrectomized or vitrectomized.
Key inclusion criteria (4 listed)
- at least 18 years of age with either type 1 or type 2 diabetes mellitus;
- maximal central subfield foveal thickness (CSF) of at least 300μm (according to SD-OCT images - Spectral Domain Optical Coherence Tomography);
- BCVA of 20 to 80 letters, using ETDRS letters chart;
- ability to provide written informed consent.
Key exclusion criteria (19 listed)
- Pregnant or lactating;
- Epiretinal membrane (ERM) existence in the study eye;
- persistent posterior hyaloid adherence after vitrectomy for group 2;
- previous vitrectomy for group 1;
- history of other retinal vascular diseases in the study eye;
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 |
|---|---|---|
| Ranibizumab 0.5 MG/0.05 ML Intraocular Solution [LUCENTIS]PRN regimen. Treatment Schedule Repeat injections at every 4-week visit if eye "improves" or "worsens" (defined as ≥5 letter change from last injection or ≥10% CST change on OCT from last injection or CSF>300 μm at any timepoint). Defer injections if either BCVA of 85 letters and OCT CSF "normal" (CSF≤300 μm and non-existent intra- or sub-retinal fluid); or OCT CSF "normal" (CSF≤300 μm) and stable BCVA (defined as < 5 letters change from last injection) after two consecutive injections during the first 24 weeks, or after one injection if the initial stability period has already been achieved (OCT CSF "normal" and stable BCVA). Resume injections if BCVA or OCT worsens. | Drug | non vitrectomized eyes, vitrectomized eyes |
Primary outcome
assess the number of IV injections needed to control DME between groups
Time frame: 18 months
DME control is defined as 1) BCVA of 85 letters and OCT CFT "normal" (CFT≤300 μm and non-existent intra- or sub-retinal fluid); or 2) OCT CFT "normal" (CFT≤300 μm) and stable BCVA (defined as <5 letters change from last injection) after two consecutive injections during the first 24 weeks, or after one injection if the initial stability period has already been achieved (OCT CFT "normal" and stable BCVA).
5 secondary outcomes
compare the functional changes at the end of follow-up between groups
Time frame: 18 months
compare the anatomical changes at the end of follow-up between groups
Time frame: 18 months
compare the percentage of type of responder during the follow-up period between groups
Time frame: 18 months
access the percentage, in group 2, of focal VMA and PVD status and type of response
Time frame: 18 months
assess retinal layers thickness as prognostic and pathophysiological biomarkers of DME treatment response
Time frame: 18 months
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 14 May 2020.
- Derived from this study: PubMed 37919940Pessoa B, Leite J, Ferreira A, Ramalhao J, Pocas J, Jose D, Coelho C, Figueira J, Meireles A, Beirao JM. Oct biomarkers for early prognosis in diabetic macular edema treatment with ranibizumab. Eur J Ophthalmol. 2024 Jul;34(4):1141-1148. doi: 10.1177/11206721231210753. Epub 2023 Nov 3.
- Derived from this study: PubMed 34845300Pessoa B, Leite J, Heitor J, Coelho J, Monteiro S, Coelho C, Figueira J, Meireles A, Melo-Beirao JN. Vitrectomized versus non-vitrectomized eyes in diabetic macular edema response to ranibizumab-retinal layers thickness as prognostic biomarkers. Sci Rep. 2021 Nov 29;11(1):23055. doi: 10.1038/s41598-021-02532-4.
- Derived from this study: PubMed 34675476Pessoa B, Marques JH, Leite J, Silva N, Jose D, Coelho C, Figueira J, Meireles A, Melo-Beirao JN. Choroidal Blood Flow After Intravitreal Ranibizumab in Vitrectomized and Non-Vitrectomized Eyes with Diabetic Macular Edema. Clin Ophthalmol. 2021 Oct 9;15:4081-4090. doi: 10.2147/OPTH.S325037. eCollection 2021.
- Individual participant dataSharing planned: No
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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.
Bernardete Pessoa, MD principal investigator
Centro Hospitalar do Porto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetic Macular Edema, run by Centro Hospitalar do Porto at 1 site in Portugal.
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 4 inclusion and 19 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 14 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Portugal. 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.
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?
assess the number of IV injections needed to control DME between groups (time frame: 18 months). 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 NCT04387604, which also lists 3 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 14 May 2020.