A Phase 4 interventional study of Ranibizumab and Grid&Direct short pulse laser photocoagulation in Macular Edema Secondary to Branch Retinal Vein Occlusion (BRVO), sponsored by Novartis Pharmaceuticals. Completed at 7 sites in Japan. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2020-02-25.
Sponsored by Novartis Pharmaceuticals · Phase 4, Interventional, and Treatment
This is a Phase IV, randomized, open-label, active-controlled, 2-arm, multicenter study. The primary objective was assessed by the difference in the mean number of ranibizumab injections applied up to Month 11 between the 2 treatment arms. Patients were randomized in a 1:1 ratio to 1 of the 2 treatment arms; i.e. Arm 1 ranibizumab monotherapy, Arm 2 ranibizumab with Grid\&Direct short pulse laser photocoagulation combination therapy. There were 3 periods in this study: Screening Period (visit 1), Treatment Period (visit 2 to Visit 13) and Follow-up Period (visit 14). In addition to screening and Baseline (visit 2), there were monthly visits from Month 1 to Month 12. This study included male and female patients (≥20 years old) diagnosed with visual impairment due to ME secondary to BRVO.
3,517 studies on the registry are indexed under Neoplasm Metastasis; 885 are open to participants now.
This study's enrollment of 59 is close to the median of 54 across 2,767 interventional studies indexed under Neoplasm Metastasis.
Browse Neoplasm Metastasis studies →Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.
Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
ranibizumab alone
Biological: Ranibizumab
ranibizumab with Grid\&Direct short pulse laser photocoagulation
Biological: Ranibizumab · Radiation: Grid&Direct short pulse laser photocoagulation
Ranibizumab is a biologic and known anti-VEGF (vascular endothelial growth factor) medication approved for treatment of ME (Macular Edema) due to RVO (Retinal Vein occlusion) 0.5 mg ranibizumab applied one + PRN as intravitreal injection of 0.05 mL, with or without laser treatment
Also known as: RFB002E
Grid\&Direct short pulse laser photocoagulation is a kind of laser treatment to retina within vascular arcades and used to suppress macular edema
Difference in Mean Number of Ranibizumab Injections
Number of ranibizumab treatments from Day 1 to Month 11 using full analysis set (observed) based on a stratified Cochran-Mantel-Haenszel (CMH) test. Stratification was done based on categories of baseline decimal VA (\<0.3, or =\>0.3). Difference of mean number of injections, 95% confidence interval (CI) of difference and one-sided p-value of the CMH test was reported. Analysis was conducted within the FAS with observed data. Stratification was based on baseline visual acuity on logMAR scale (\<0.52, \>=0.52). Test was one-sided.
Time frame: Month 1 through Month 12
The Mean Change in Best Corrected Visual Acuity (BCVA) Using Decimal Chart and Early Treatment Diabetic Retinopathy Study (ETDRS) Compared to Baseline
Summary of BCVA (letters) absolute value and change from Baseline at Month 12 in the study eye - full analysis set (LOCF) was based on an analysis of variance (ANOVA) model with treatment group, and stratification factors. Stratification was done based on categories of baseline decimal VA (\<0.3, or =\>0.3). The analyses was conducted within the FAS using the LOCF approach Stratification was based on baseline visual acuity on logMAR scale (\<0.52, \>=0.52). Test was one-sided.
Time frame: Month 1 through Month 12 (for ETDRS: Month 6 and Month 12)
The Mean Change in BCVA From Month 1 Through Month 12 Compared to Baseline (Day 1) by the Treatment Arms
Summary of BCVA (logMAR) absolute value and change from Baseline at Month 12 in the study eye - full analysis set (LOCF) was based on an analysis of variance (ANOVA) model with treatment group, and stratification factors. Stratification was based on baseline visual acuity (\< 0.52, \>= 0.52). The analyses was conducted within the FAS using the LOCF approach
Time frame: Month 1 through Month 12
BCVA (Letters) Number and Proportion of Patients With a BCVA Improvement vs. Baseline, Loss Less Than 15 Letters, or Attainment of Greater Than or Equal to 85 Letters at Month 6 and at Month 12 in the Study Eye
Endpoints related to the number and proportion of patients with BCVA letter gain or loss from Baseline (Day1) was analyzed via stratified CMH test with stratification factors as described in primary model. The mean (SD) average (per patient) BCVA (logMAR) change from Baseline through Month 12 Summary of BCVA (logMAR) mean average change from Baseline from Month 1 through Month 12 in the study eye
Time frame: Month 6 and Month 12
The Mean Change in Change in Central Subfield Foveal Thickness (CSFT) From Month 1 Through Month 12 Compared to Baseline (Day1) by the Treatment Arms
The mean change in investigator-assessed CSFT from Month 1 through Month 12 was compared to Baseline (Day1) by the treatment arms. The analyses at each visit was based on an analysis of variance (ANOVA) model as analogous to BCVA. The analyses was conducted within the FAS using the Last-Observation-Carried-Forward (LOCF) approach
Time frame: Month 1 through Month 12
73 patients were screened and 59 were randomized on a 1:1 ratio to the ranibizumab group (29 patients) and ranibizumab with laser group (30 patients). Of the randomized patients, 56 (94.9%) completed the study and 11 months of treatment. 3 (5.1%) discontinued both study and study treatment: 2 (3.4%) withdrew consent and 1 (1.7%) had adverse event
| Milestone | Ranibizumab 0.5 mg | Ranibizumab 0.5 mg and Laser |
|---|---|---|
| Started | 29 | 30 |
| Completed | 28 | 28 |
| Not completed | 1 | 2 |
| Withdrew: Adverse event | 0 | 1 |
| Withdrew: Withdrawal by subject | 1 | 1 |
Number of ranibizumab treatments from Day 1 to Month 11 using full analysis set (observed) based on a stratified Cochran-Mantel-Haenszel (CMH) test. Stratification was done based on categories of baseline decimal VA (\<0.3, or =\>0.3). Difference of mean number of injections, 95% confidence interval (CI) of difference and one-sided p-value of the CMH test was reported. Analysis was conducted within the FAS with observed data. Stratification was based on baseline visual acuity on logMAR scale (\<0.52, \>=0.52). Test was one-sided.
| number of injections | Ranibizumab 0.5 mg | Ranibizumab 0.5 mg Laser |
|---|---|---|
| Difference in Mean Number of Ranibizumab Injections | 4.3 ± 2.51 | 4.1 ± 2.41 |
Summary of BCVA (letters) absolute value and change from Baseline at Month 12 in the study eye - full analysis set (LOCF) was based on an analysis of variance (ANOVA) model with treatment group, and stratification factors. Stratification was done based on categories of baseline decimal VA (\<0.3, or =\>0.3). The analyses was conducted within the FAS using the LOCF approach Stratification was based on baseline visual acuity on logMAR scale (\<0.52, \>=0.52). Test was one-sided.
| letters read correctly | Ranibizumab 0.5 mg | Ranibizumab 0.5 mg Laser |
|---|---|---|
| baseline | 52.86 ± 13.384 | 54.03 ± 9.828 |
| month 12 | 74.83 ± 9.740 | 69.59 ± 8.842 |
| change from baseline to month 12 | 21.97 ± 14.749 | 15.00 ± 10.296 |
Summary of BCVA (logMAR) absolute value and change from Baseline at Month 12 in the study eye - full analysis set (LOCF) was based on an analysis of variance (ANOVA) model with treatment group, and stratification factors. Stratification was based on baseline visual acuity (\< 0.52, \>= 0.52). The analyses was conducted within the FAS using the LOCF approach
| logMAR | Ranibizumab 0.5 mg | Ranibizumab 0.5 mg Laser |
|---|---|---|
| baseline | 0.553 ± 0.2276 | 0.558 ± 0.1719 |
| month12 | 0.075 ± 0.1909 | 0.143 ± 0.1682 |
| change from baseline to month 12 | -0.478 ± 0.2586 | -0.413 ± 0.1969 |
Endpoints related to the number and proportion of patients with BCVA letter gain or loss from Baseline (Day1) was analyzed via stratified CMH test with stratification factors as described in primary model. The mean (SD) average (per patient) BCVA (logMAR) change from Baseline through Month 12 Summary of BCVA (logMAR) mean average change from Baseline from Month 1 through Month 12 in the study eye
| Participants | Ranibizumab 0.5 mg | Ranibizumab 0.5 mg Laser |
|---|---|---|
| Month 6 - BCVA improvement of >=1 | 27 | 24 |
| month 6 - BCVA improvement of >=5 | 26 | 21 |
| month 6 - BCVA improvement of >=10 | 22 | 16 |
| Month 6 - BCVA improvement of >=15 | 17 | 12 |
| Month 6 - BCVA improvement of >=30 | 4 | 1 |
| month 6 Score >=73 | 12 | 10 |
| month 6 Score >=80 | 8 | 2 |
| month 6 Score >=85 | 3 | 1 |
| month 6 loss of <15 | 28 | 29 |
| Month 12 - BCVA improvement of >=1 | 27 | 28 |
| Month 12 - BCVA improvement of >=5 | 27 | 25 |
| Month 12 - BCVA improvement of >=10 | 24 | 18 |
| Month 12 - BCVA improvement of >=15 | 21 | 15 |
| Month 12 - BCVA improvement of >=30 | 9 | 3 |
| month 12 Score >=73 | 20 | 10 |
| month 12 Score >=80 | 8 | 13 |
| month 12 Score >=85 | 4 | 0 |
| month 12 Loss of <15 | 29 | 29 |
The mean change in investigator-assessed CSFT from Month 1 through Month 12 was compared to Baseline (Day1) by the treatment arms. The analyses at each visit was based on an analysis of variance (ANOVA) model as analogous to BCVA. The analyses was conducted within the FAS using the Last-Observation-Carried-Forward (LOCF) approach
| mm | Ranibizumab 0.5 mg | Ranibizumab 0.5 mg Laser |
|---|---|---|
| baseline | 563.3 ± 146.92 | 553.3 ± 182.39 |
| month 12 | 257.0 ± 43.44 | 285.1 ± 82.80 |
| change in baseline from month 12 | -306.3 ± 164.35 | -261.3 ± 180.23 |
Collected over AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 12 months.. Non-serious events are listed at a 2% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ranibizumab 0.5 mg | 0/29 (0%) | 1/29 (3.4%) | 16/29 (55.2%) |
| Ranibizumab 0.5 mg+ Laser | 0/30 (0%) | 2/30 (6.7%) | 15/30 (50%) |
| Total | 0/59 (0%) | 3/59 (5.1%) | 31/59 (52.5%) |
| Event | Ranibizumab 0.5 mg | Ranibizumab 0.5 mg+ Laser | Total |
|---|---|---|---|
| HaematuriaRenal and urinary disorders | 1/29 | 0/30 | 1/59 |
| Bowen's diseaseNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/29 | 1/30 | 1/59 |
| Putamen haemorrhageNervous system disorders | 0/29 | 1/30 | 1/59 |
| Event | Ranibizumab 0.5 mg | Ranibizumab 0.5 mg+ Laser | Total |
|---|---|---|---|
| NasopharyngitisInfections and infestations | 6/29 | 5/30 | 11/59 |
| HeadacheNervous system disorders | 3/29 | 0/30 | 3/59 |
| Intraocular pressure increasedInvestigations | 0/29 | 3/30 | 3/59 |
| NauseaGastrointestinal disorders | 2/29 | 1/30 | 3/59 |
| HypertensionVascular disorders | 2/29 | 1/30 | 3/59 |
| Dry eyeEye disorders | 1/29 | 1/30 | 2/59 |
| KeratitisEye disorders | 1/29 | 0/30 | 1/59 |
| Hepatic function abnormalHepatobiliary disorders | 1/29 | 0/30 | 1/59 |
| Seasonal allergyImmune system disorders | 1/29 | 1/30 | 2/59 |
| InfluenzaInfections and infestations | 1/29 | 1/30 | 2/59 |
Randomized Set
| Age, Continuous(years) | Ranibizumab 0.5 mg | Ranibizumab 0.5 mg and Laser | Total |
|---|---|---|---|
| Mean | 66.8 ± 9.91 | 66.7 ± 9.83 | 66.8 ± 9.78 |
| Age, Customized(Participants) | Ranibizumab 0.5 mg | Ranibizumab 0.5 mg and Laser | Total |
|---|---|---|---|
| <65 years | 12 | 11 | 23 |
| >=65 years | 17 | 19 | 36 |
| Sex: Female, Male(Participants) | Ranibizumab 0.5 mg | Ranibizumab 0.5 mg and Laser | Total |
|---|---|---|---|
| Female | 10 | 19 | 29 |
| Male | 19 | 11 | 30 |
| Race/Ethnicity, Customized(Participants) | Ranibizumab 0.5 mg | Ranibizumab 0.5 mg and Laser | Total |
|---|---|---|---|
| Asian | 29 | 30 | 59 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Undecided — Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
This study is completed, as verified in Feb 2020. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Novartis Pharmaceuticals