UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Ranibizumab Exploratory Study on the Evaluation of the local laser combination therapy to non-reactive group to the diabetic macular edema patients
Title of the study (Brief title)	RELAND study
Region	Japan

Condition
Condition	Diabetic Macular edema
Classification by specialty	Ophthalmology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the effect of ranibizumab and additional focal laser with ranibizumab for DME treatment
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	The mean change from baseline in best corrected visual acuity (BCVA) at 6 month
Key secondary outcomes	The mean change from baseline in central retinal thickness (CRT) based on SD-OCT at 6 month. The number of injections, and the number of laser treatment at 6 month.

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Active
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	3
Purpose of intervention	Treatment
Type of intervention	Device,equipment Maneuver
Interventions/Control_1	This is a 6 months, prospective, interventional, exploratory, consecutive case series study, and followed by 6 months extension. Patients receive ranibizumab once a month during first two months. After three consecutive monthly injection of ranibizumab, patients are classified into two groups: "Initial responder" and "Initial non-responder". Initial responder is defined that an improvement of more than 5 letters in BCVA or a decrease of at least 20% in CRT from baseline. 1)Initial responder: After three monthly injections, ranibizumab treatment is continued until macula becomes dry (Dry means CRT=<250um). After that, the injection is continued pro re nata (PRN) regimen. (Retreatment criteria of intravitreal ranibizumab is CRT=>250um) 2)Initial non-responder: After three consecutive monthly injections, FA is performed to clarify the vascular leak from microaneurysm close to macula edema or avascular area at Month 3 visit. Patients are treated with additional focal laser to microaneurysm and avascular area in edema region by judging from FA, fundus photograph and SD-OCT at this visit, if these regions are applicable for focal laser. After focal laser, ranibizumab injection is given at this visit followed by ranibizumab injections by same manner in "initial responder". Otherwise, if focal laser is not applicable to the regions based on the examinations, patients receive ranibizumab injections by similar manner in "initial responder". Focal laser treatment is able to be performed at intervals no shorter than 3 months from the first focal laser. Laser condition: power80-100mA, spot size 50-100um, duration 0.1second, Area Centralis/TransEquater as lens. Fundus condition has to be estimated by FA, SD-OCT and fundus photograph during examination. If patient lose therapeutic effect during only ranibizumab therapy, focal laser have to be performed after examination.
Interventions/Control_2	This is a 6 months, prospective, interventional, exploratory, consecutive case series study, and followed by 6 months extension. Patients receive ranibizumab once a month during first two months. After three consecutive monthly injection of ranibizumab, patients are classified into two groups: "Initial responder" and "Initial non-responder". Initial responder is defined that an improvement of more than 5 letters in BCVA or a decrease of at least 20% in CRT from baseline. 1)Initial responder: After three monthly injections, ranibizumab treatment is continued until macula becomes dry (Dry means CRT=<250um). After that, the injection is continued pro re nata (PRN) regimen. (Retreatment criteria of intravitreal ranibizumab is CRT=>250um) 2)Initial non-responder: After three consecutive monthly injections, FA is performed to clarify the vascular leak from microaneurysm close to macula edema or avascular area at Month 3 visit. Patients are treated with additional focal laser to microaneurysm and avascular area in edema region by judging from FA, fundus photograph and SD-OCT at this visit, if these regions are applicable for focal laser. After focal laser, ranibizumab injection is given at this visit followed by ranibizumab injections by same manner in "initial responder". Otherwise, if focal laser is not applicable to the regions based on the examinations, patients receive ranibizumab injections by similar manner in "initial responder". Focal laser treatment is able to be performed at intervals no shorter than 3 months from the first focal laser. Laser condition: power80-100mA, spot size 50-100um, duration 0.1second, Area Centralis/TransEquater as lens. Fundus condition has to be estimated by FA, SD-OCT and fundus photograph during examination. If patient lose therapeutic effect during only ranibizumab therapy, focal laser have to be performed after examination.
Interventions/Control_3	This is a 6 months, prospective, interventional, exploratory, consecutive case series study, and followed by 6 months extension. Patients receive ranibizumab once a month during first two months. After three consecutive monthly injection of ranibizumab, patients are classified into two groups: "Initial responder" and "Initial non-responder". Initial responder is defined that an improvement of more than 5 letters in BCVA or a decrease of at least 20% in CRT from baseline. 1)Initial responder: After three monthly injections, ranibizumab treatment is continued until macula becomes dry (Dry means CRT=<250um). After that, the injection is continued pro re nata (PRN) regimen. (Retreatment criteria of intravitreal ranibizumab is CRT=>250um) 2)Initial non-responder: After three consecutive monthly injections, FA is performed to clarify the vascular leak from microaneurysm close to macula edema or avascular area at Month 3 visit. Patients are treated with additional focal laser to microaneurysm and avascular area in edema region by judging from FA, fundus photograph and SD-OCT at this visit, if these regions are applicable for focal laser. After focal laser, ranibizumab injection is given at this visit followed by ranibizumab injections by same manner in "initial responder". Otherwise, if focal laser is not applicable to the regions based on the examinations, patients receive ranibizumab injections by similar manner in "initial responder". Focal laser treatment is able to be performed at intervals no shorter than 3 months from the first focal laser. Laser condition: power80-100mA, spot size 50-100um, duration 0.1second, Area Centralis/TransEquater as lens. Fundus condition has to be estimated by FA, SD-OCT and fundus photograph during examination. If patient lose therapeutic effect during only ranibizumab therapy, focal laser have to be performed after examination.
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1) patients who have diabetes, and have developed in at least one eye diabetic macular edema Patients 2) does not recognize the acute myocardial infarction and cerebral infarction within the onset 3 months Patient age is greater than or equal to 20 years of age at the time of 3) obtaining informed consent 4) gender unquestioned 5) After having received a sufficient explanation Upon participation in the present study, patients on the full understanding, the document agreed by the free will of the patient himself was obtained 6) hospitalization, outpatient unquestioned
Key exclusion criteria	1) Patients with a treatment history of anti VEGF drugs patients 2) Patients with infection or infection suspictions in the eye or around the eye 3) Patients with severe inflammation in the eye 4) DME disease duration is more than 12 months 5) Patients who underwent direct photocoagulation to 3 months in DME within 1000um from the fovea 6) Patients who underwent triamcinolone acetonide subtenon injection or triamcinolone acetonide intravitreal injectionwithin 3 months 7) Patients who underwent PRP within 6 months 8) HbA1c is over 10.0% 9) Poor control of hypertension 10) Eye surgery within 6 months 11) ranibizumab or to the components of other anti-VEGF drugs, those with a history of hypersensitivity 12) Pregnancy, in nursing 13) Other, patient research responsibility who is determined to be unsuitable as research subjects
Target sample size	100

Research contact person
Name of lead principal investigator	Kazuhiro Kimura
Organization	Department of Ophthalmology, Yamaguchi University Graduate School of Medicine
Division name	opthalmology
Address	1-1-1 Minami-Kogushi, Ube City Yamaguchi 755-8505, Japan
TEL	0836-22-2278
Email	k.kimura@yamaguchi-u.ac.jp

Public contact
Name of contact person	Kazuhiro Kimura
Organization	Department of Ophthalmology, Yamaguchi University Graduate School of Medicine
Division name	opthalmology
Address	1-1-1 Minami-Kogushi, Ube City Yamaguchi 755-8505, Japan
TEL	0836-22-2278
Homepage URL
Email	k.kimura@yamaguchi-u.ac.jp

Sponsor
Institute	Yamaguchi University
Institute
Department

Funding Source
Organization	Novartis Pharmaceuticals Japan
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2016 Year 11 Month 18 Day

Progress
Recruitment status	Open public recruiting
Date of protocol fixation	2016 Year 06 Month 14 Day
Anticipated trial start date	2016 Year 10 Month 01 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2016 Year 09 Month 28 Day
Last modified on	2018 Year 10 Month 01 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000027867