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Enrollment pace was far below target.
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| Name | Class |
|---|---|
| Charite University, Berlin, Germany | OTHER |
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The aim of the prospective randomized study is to investigate whether a intensified diabetic control program leads to better final visual acuity and less frequent diabetic ocular complications in patients with diabetic retinopathy when compared with a normal diabetic treatment.
Patients with diabetic macular edema (DME) will be treated with intravitreal ranibizumab injections and the effect of optimal control of internal factors (eg. glycemia, blood pressure etc) on final functional (best corrected visual acuity-CBVA) and morphological (central retinal thickness-CRT) will be investigated. Patients will be randomized into two groups: Group with intensified diabetic control will be follow and investigated monthly at department of diabetology, endocrinology and nutritional medicine (Campus Benjamin Franklin) in Berlin with aim to reach the optimal glycemic control defined as HbA1c < 6,5%. Further, triglycerides values < 140 mg/dl and blood pressure < 140/90 mmHg will be pursued. Second group of patients will be followed by their general practitioner and in the study center only blood samples will be taken quarterly without active medical intervention.
BCVA, CRT and the number of required ranibizumab injections will we evaluated and compared between both study groups.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Regular Glycemic Control | Active Comparator | Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control. |
|
| Intensified Glycemic Control | Experimental | Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level < 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ranibizumab | Drug | Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Difference of Best Corrected Visual Acuity Measured in ETDRS Letters Score Between Month 12 Baseline Visit | Measured by the difference in ETDRS letters score between month 12 and baseline according to internal guideline of Charité department of ophthalmology. | Baseline to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Treatments With Ranibizumab up to 6, 12, 18 and 24 Months of Treatment | For the number of treatments at 6, 12, 18 and 24 months, an ANOVA without any covariates was planned to be applied at each endpoint 6, 12, 18 and 24 months. As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus statistical analysis of the endpoint was waived completely. None of the patients reached time points beyond month 12. Results are only shown descriptively. Ranibizumab injections were summed up per study arm as well as cumulative at each time point. |
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Inclusion Criteria:
- Patients with diabetic macular edema relevant to visual acuity
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Ophthalmology, Charite, Berlin | Berlin | 12203 | Germany |
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Screening period of seven days prior to randomization.
The recruitment has been stopped prematurely in August 2018 by the sponsor after the enrolment of four patients because the enrollment pace was far below target.
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| ID | Title | Description |
|---|---|---|
| FG000 | Regular Glycemic Control | Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied. |
| FG001 | Intensified Glycemic Control | Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level < 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Regular Glycemic Control | Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Difference of Best Corrected Visual Acuity Measured in ETDRS Letters Score Between Month 12 Baseline Visit | Measured by the difference in ETDRS letters score between month 12 and baseline according to internal guideline of Charité department of ophthalmology. | Of the four enrolled patients, only the two patients had 12-month visit. Since the time point for the evaluation of the primary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus analysis of the primary endpoint was waived. | Posted | Baseline to 12 months |
|
First administration of the IMP until 30 days after the patient has stopped the treatment. Treatment is given individually acc. to summary of product characteristics following a pro re nata (as needed) scheme. Therefore adverse event data will be collected until time points individually for each patient but not longer than total trial duration (24 months). Time frame per protocol was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Regular Glycemic Control | Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled by their general practitioner or private diabetologist (usual care). The glycemic control (blood measurements of HbA1c) will be performed at trial site (Department of diabetology, endocrinology and nutritional medicine) every 3 months. The site will not influence or change the diabetes medication given by general physician and serves as an observer only to monitor the diabetic control. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertensive crisis | Vascular disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment |
Recruitment was stopped prematurely by the sponsor after enrolment of four patients since enrollment pace was far below target. Due to the limited number of patients, no conclusions in respect to the study aims can be made.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Dr. Antonia Joussen | Charité University, Berlin | +49 30 84452331 | antonia.joussen@charite.de |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 23, 2015 | May 31, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D008269 | Macular Edema |
| ID | Term |
|---|---|
| D008268 | Macular Degeneration |
| D012162 | Retinal Degeneration |
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| D000069579 | Ranibizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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Observer-masking (assessment of BCVA, macular thickness, capillary drop-out) is done to guard against detection bias.
| Baseline to 12 months |
| Difference of Best Corrected Visual Acuity Measured in ETDRS Letters Score Between Month 6, 12, 24 and Baseline Visit | As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus analysis of the endpoint was waived completely. Time point 24 months was reached by none of the patients due to trial discontinuation. Results are only shown descriptively. Best-corrected visual acuity (BCVA) score is shown as change in ETDRS letters score at the distinct time point compared to baseline. Higher scores mean a better outcome. | Baseline to 12 months |
| Macular Thickness Change at 6, 12, 18 and 24 Months Compared to Baseline | As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus analysis of the endpoint was waived completely. None of the patients reached time points beyond month 12 due to trial discontinuation. Results are only shown descriptively. Macular thickness (study eye) is shown as change in thickness [µm] compared to individual baseline value. A reduction in thickness means improvement. | Baseline to 12 months |
| Time to Reach Target HbA1c | 24 months |
| Number of Panretinal Laser Photocoagulation (PRP) Treatments Necessary for Neovascular Complications | Need for PRP is up to the investigator's decision. Assessment was done on every visit. Intended time frame was baseline to 24 months. None of the patients reached time points beyond month 12 due to study discontinuation. Unit of measure is any separate investigator's decision to perform panretinal laser photocoagulation (PRP) for neovascular complications. Each PRP is counted separately. | Baseline to 12 months |
| Number of Participants With Retinal Detachment, Central Retinal Artery Occlusion, or Endophthalmitis and/or Ocular Adverse Events That Are Related to Treatment | All ocular adverse events presented from baseline to 24 months will be documented. | Baseline to 12 months |
| Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment | All adverse events were documented. Causal relationship to study treatment was assessed by the investigators. Intended time frame was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation. | Baseline to 12 months |
| Lost to Follow-up |
|
| BG001 | Intensified Glycemic Control | Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level < 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Number of participants with history of ophthalmic disease | Ophthalmic history features were collected (previous ophthalmic surgery, ocular trauma, glasses, glaucoma, glaucoma treatment, amblyopia, history of diabetic retinopathy). | Count of Participants | Participants |
|
| Number of patients with medical history | Medical history was determined (allergy, allergy medication, hypertonia, hypertonia medical compensation, hyperlipidemia, smoking, insulin treatment). | Count of Participants | Participants |
|
| OG001 | Intensified Glycemic Control | Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level < 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied. |
|
| Secondary | Number of Treatments With Ranibizumab up to 6, 12, 18 and 24 Months of Treatment | For the number of treatments at 6, 12, 18 and 24 months, an ANOVA without any covariates was planned to be applied at each endpoint 6, 12, 18 and 24 months. As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus statistical analysis of the endpoint was waived completely. None of the patients reached time points beyond month 12. Results are only shown descriptively. Ranibizumab injections were summed up per study arm as well as cumulative at each time point. | At month 6, the two patients in study arm A had received six treatments each; the two patients in study arm B had received three and five treatments, respectively. At month 12, the two patients in study arm B had received three and six treatments, respectively. For none of the patients in study arm A, 12-month data was available. | Posted | Number | Ranibizumab injections | Baseline to 12 months |
|
|
|
| Secondary | Difference of Best Corrected Visual Acuity Measured in ETDRS Letters Score Between Month 6, 12, 24 and Baseline Visit | As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus analysis of the endpoint was waived completely. Time point 24 months was reached by none of the patients due to trial discontinuation. Results are only shown descriptively. Best-corrected visual acuity (BCVA) score is shown as change in ETDRS letters score at the distinct time point compared to baseline. Higher scores mean a better outcome. | BCVA score compared to baseline. | Posted | Number | Letters improved | Baseline to 12 months |
|
|
|
| Secondary | Macular Thickness Change at 6, 12, 18 and 24 Months Compared to Baseline | As the time point 12 months for the evaluation of this secondary endpoint was reached only for patients of study arm B, a comparison of both study arms was not possible and thus analysis of the endpoint was waived completely. None of the patients reached time points beyond month 12 due to trial discontinuation. Results are only shown descriptively. Macular thickness (study eye) is shown as change in thickness [µm] compared to individual baseline value. A reduction in thickness means improvement. | For none of the patients in study arm A 12-month data was available. Time points beyond 6 months (18, 24 months) were reached by none of the patients due to trial discontinuation. Results are only shown descriptively. | Posted | Number | µm | Baseline to 12 months |
|
|
|
| Secondary | Time to Reach Target HbA1c | Originally, target HbA1c should have been defined individually for each patient by the investigator acc. to the patient's general status by risk factors for vasculopathy (Body-Mass-Index, smoking, blood pressure, lipid Status). However, definition of target HbA1c values was waived and only HbA1c values were documented (not shown here). | Posted | 24 months |
|
|
| Secondary | Number of Panretinal Laser Photocoagulation (PRP) Treatments Necessary for Neovascular Complications | Need for PRP is up to the investigator's decision. Assessment was done on every visit. Intended time frame was baseline to 24 months. None of the patients reached time points beyond month 12 due to study discontinuation. Unit of measure is any separate investigator's decision to perform panretinal laser photocoagulation (PRP) for neovascular complications. Each PRP is counted separately. | Posted | Number | number of PRPs across participants | Baseline to 12 months |
|
|
|
| Secondary | Number of Participants With Retinal Detachment, Central Retinal Artery Occlusion, or Endophthalmitis and/or Ocular Adverse Events That Are Related to Treatment | All ocular adverse events presented from baseline to 24 months will be documented. | Patients in study arm A discontinued before month 12. None of the patients reached time points beyond month 12 due to trial discontinuation. | Posted | Number | participants | Baseline to 12 months |
|
|
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| Secondary | Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment | All adverse events were documented. Causal relationship to study treatment was assessed by the investigators. Intended time frame was baseline to 24 months. None of the patients reached time points beyond 12 months due to study discontinuation. | Posted | Number | participants | Baseline to 12 months |
|
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|
| 0 |
| 2 |
| 1 |
| 2 |
| 2 |
| 2 |
| EG001 | Intensified Glycemic Control | Diabetic macular edema will be treated with 3 monthly ranibizumab (0,5mg) injections followed by PRN regimen. Patients randomized into this group will be controlled at the trial site (Department of diabetology, endocrinology and nutritional medicine) during first year monthly, in the second study year every 3 months. The individual HbA1c will be targeted according to the general status reflecting other risk factors for the vasculopathy (e.g. BMI, smoking, blood pressure, lipid status). All effort will be done to reach the target blood pressure ≤ 140/90 mmHg and blood triglyceride level < 140 mg/dl: Further the patients will be educated to improve their eating habits in regard to reduce the carbohydrate intake. ranibizumab: Ranibizumab injections will be given for diabetic macular edema. In the experimental arm insulin injections and antihypertensiva will be applied. | 0 | 2 | 1 | 2 | 2 | 2 |
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Blood pressure increased | Investigations | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
|
| Otosalpingitis | Infections and infestations | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Coronary artery disease | Cardiac disorders | Systematic Assessment |
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| Bronchitis | Infections and infestations | Systematic Assessment |
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| Chest pain | General disorders | Systematic Assessment |
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| Diabetic retinal oedema | Eye disorders | Systematic Assessment |
|
| Diabetic retinopathy | Eye disorders | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
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| Exostosis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Eye pain | Eye disorders | Systematic Assessment |
|
| Foreign body sensation in eyes | Eye disorders | Systematic Assessment |
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| Heart valve stenosis | Cardiac disorders | Systematic Assessment |
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| Injection site pain | General disorders | Systematic Assessment |
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| Injury associated with device | General disorders | Systematic Assessment |
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| Macular oedema | Eye disorders | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Night sweats | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Oedema peripheral | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | Systematic Assessment |
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| Retinal exudates | Eye disorders | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Ocular discomfort | Eye disorders | Systematic Assessment |
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| Blepharitis | Eye disorders | Systematic Assessment |
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| Anterior chamber disorder | Eye disorders | Systematic Assessment |
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| Conjunctival haemorrhage | Eye disorders | Systematic Assessment |
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| Device dislocation | Product Issues | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | Systematic Assessment |
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| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| Month 12 |
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| Participant 2, month 6 |
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| Participant 3, month 6 |
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| Participant 4, month 6 |
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| Participant 3, month 12 |
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| Participant 4, month 12 |
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| Participant 2, month 6 |
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| Participant 3, month 6 |
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| Participant 4, month 6 |
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| Participant 1, month 12 |
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| Participant 2, month 12 |
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| Participant 3, month 12 |
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| Participant 4, month 12 |
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| Month 12 |
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