UMIN-CTR Clinical Trial

Public title

Ranibizumab Exploratory Study on the Evaluation of the local laser combination therapy to non-reactive group to the diabetic macular edema patients

Acronym

RELAND study

Scientific Title

Ranibizumab Exploratory Study on the Evaluation of the local laser combination therapy to non-reactive group to the diabetic macular edema patients

Scientific Title:Acronym

RELAND study

Region

Japan

Condition

Diabetic Macular edema

Classification by specialty

Ophthalmology

Classification by malignancy

Others

Genomic information

NO

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

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.

Study type

Interventional

Basic design

Parallel

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Kazuhiro Kimura

Organization

Department of Ophthalmology, Yamaguchi University Graduate School of Medicine

Division name

opthalmology

Zip code

Address

1-1-1 Minami-Kogushi, Ube City Yamaguchi 755-8505, Japan

TEL

0836-22-2278

Email

k.kimura@yamaguchi-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Kazuhiro Kimura

Organization

Department of Ophthalmology, Yamaguchi University Graduate School of Medicine

Division name

opthalmology

Zip code

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

Institute

Yamaguchi University

Institute

Department

Personal name

Organization

Novartis Pharmaceuticals Japan

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2016

Year

11

Month

18

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2016

Year

06

Month

14

Day

Date of IRB

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

Other related information

Registered date

2016

Year

09

Month

28

Day

Last modified on

2018

Year

10

Month

01

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027867