UMIN-CTR Clinical Trial

Public title

Lymphatic Venous Anastomosis for secondary lymphedema -Randamized Control Trial-

Acronym

LVA for secondary lymphedema

Scientific Title

Lymphatic Venous Anastomosis for secondary lymphedema -Randamized Control Trial-

Scientific Title:Acronym

LVA for secondary lymphedema

Region

Japan

Condition

Secondary lymphedema

Classification by specialty

Surgery in general

Plastic surgery

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

This study is a randomized controlled trial of LVA and nonsurgical therapy.
We evaluate and compare lymphoedema improvement and deterioration by randomly assigning LVA and nonsurgical therapy to patients who visited JR Tokyo General Hospital lymphatic surgery / reconstructive surgery and observing for 6 months.
Currently, the effect of LVA on lymphoedema has been reported, and it can be fully expected that this clinical effect can be obtained by this research.

This study will contribute to the development of a more effective treatment method compared with the compound physiotherapy which is currently regarded as standard treatment.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Evaluate based on the change in the number of times of cellulitis. In the LVA group, the number of times of cellulitis inflammation during 24 weeks before the start of the intervention and 24 weeks after the start of the intervention is compared. In the conservative therapy group, we compare the number of times of cellulitis in 24 weeks before the allocation date and 24 weeks after the allocation date. Huigong weeping inflammation is defined as having inflammatory findings such as redness and heat sensation on the affected limb and having a fever of 38.5 degrees or more.

Key secondary outcomes

1.circumference of affected limb
Measure with six tapes of 20 cm above the knee, 10 cm above the knee, knee joint, 10 cm below the knee, ankle joint and foot sole, and calculate the rate of change based on the following formula. Measurement is blinded by doing a nurse or a physical therapist who is not involved in surgery and research protocol creation.
Change rate (%) = (Sum of surrounding diameters after operation - Sum of surrounding diameters before surgery) / Sum of peripheral diameter before surgery x 100

2.Pain, discomfort (subjective symptoms)
Record using visual analogue scale (VAS).

3.Subcutaneous tissue hardness
Three types of urethane sponge with different hardness (Yawata Tayzen Co., Ltd.) are used to compare this with the firmness of the skin and subcutaneous tissue of the affected limb by palpation. Evaluate the distal inner and outer side of the lower leg, proximal inner and outer sides of the lower limb, distal inner and outer sides of the thigh, inner side of the thigh and inner side and outer side of the thigh. Each sponge is numbered 2, 4, 6 according to the hardness, 2 points if it is the same hardness as 2, 1 point if it is softer than 2, 3 points if it is hardness between 2 and 4 Evaluate in seven stages of 1 to 7 points. This evaluation is blinded by doing a nurse or a physical therapist who is not involved in surgery and research protocol creation.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Cluster

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Maneuver

Interventions/Control_1

As a surgical treatment, removal of subcutaneous tissues in which elephant-like degenerated skin and fibrosis have progressed, liposuction and the like have been carried out, but JR Tokyo General Hospital lymphatic surgery / reconstructive surgery uses supermicrosurgery technology We are actively doing lymph venous anastomosis (LVA). Internationally, vascular lymph node transplantation is performed more frequently, which seems to be mainly due to the easiness of surgical technique for transplantation with vascular lymph nodes. On the other hand, with vascular lymph node transplantation, there is a possibility that new lymphedema may occur in the lymph node harvesting section after surgery, and case reports are already being conducted at academic conferences, papers and the like.
Our LVA is a minimally invasive surgery which can be performed under local anesthesia and there is no risk of lymphoedema occurring at other sites after surgery, but it is mainly surgery developed in Japan, Currently there is little medical evidence. Internationally, randomized controlled trials on LVA have not been conducted.

Interventions/Control_2

Non-surgical treatment, complex physical therapy

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Patients who received JR Tokyo General Hospital lymphatic surgery / reconstructive surgery
2) Patients diagnosed with secondary lower extremity lymphedema by lymphoscintigraphy
3) Patients who have conservative therapy for more than 3 months already
4) Patients judged to have the ability to answer inquiries
5) Patients who obtained written consent from the patients themselves freely with sufficient understanding after receiving sufficient explanation for participation in this study.
6) In the case that the patient is a minor, 5) In addition to the case that the patient guardian fully understands and obtains written consent.

Key exclusion criteria

Patients who conflict with the following criteria shall not be included in this study.
1) Patients who can be expected to have a postoperative follow-up period of less than 6 months at JR Tokyo General Hospital, Bethel Minami Shinjuku Clinic, Medical Corporation Mihara Internal Medicine
2) Patients with complication of edema due to heart failure, renal failure, etc.
3) Cases judged inappropriate by the doctor sharing test

Target sample size

120

Name of lead principal investigator

1st name	Makoto
Middle name	-
Last name	Mihara

Organization

JR Tokyo General Hospital

Division name

Lymphatic and Reconstructive Surgery

Zip code

1518528

Address

Yoyogi 2-1-3, Shibuya-ku, Tokyo, Japan

TEL

03-3320-2200

Email

mihara.plasticsurgery@gmail.com

Name of contact person

1st name	Hisako
Middle name	-
Last name	Hara

Organization

JR Tokyo General Hospital

Division name

Lymphatic and Reconstructive Surgery

Zip code

1518528

Address

Yoyogi 2-1-3, Shibuya-ku, Tokyo, Japan

TEL

03-3320-2200

Homepage URL

Email

hisakohara.prs@gmail.com

Institute

JR tokyo general Hospital
BETHEL MINAMI-Shinjuku clinic
Mihara Interanal medicine clinic

Institute

Department

Personal name

Organization

none

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

JR Tokyo general hospital, Offce of Pharmacy

Address

Yoyogi 2-1-3, Shibuya-ku, Tokyo, Japan

Tel

0333202200

Email

06share09@jreast.co.jp

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

2018

Year

02

Month

24

Day

URL releasing protocol

https://www.mominoki-shinryosho.jp/cellulitis/evidence/

Publication of results

Published

URL related to results and publications

https://www.mominoki-shinryosho.jp/cellulitis/evidence/

Number of participants that the trial has enrolled

336

Results

Analysis
First, I will describe the results of the FAS analysis. The incidence of cellulitis over 6 months, the primary outcome, was -0.57 in the LVA group and -0.21 in the CDT group. The difference was -0.35 times (95% confidence interval: -0.62 to -0.09), and Welch's t-test showed that the cellulitis prevention effect was significantly higher in the LVA group (p = 0.010).

Results date posted

2022

Year

09

Month

24

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Target patient
Patients who underwent lymphatic surgery/reconstructive surgery at Saiseikai Kawaguchi General Hospital for the first time from 2017.1 to 2017.12 or who visited JR Tokyo General Hospital for the first time from 2018.2 to 2019.9.

The inclusion criteria are as follows.
-Patients diagnosed with secondary lower extremity lymphedema
Patients who have already received conservative treatment for more than 3 months
Patients judged to have the ability to answer medical questions

Participant flow

-Patients who have given written informed consent of their own free will after receiving a sufficient explanation for participating in this study.
If the patient is a minor, in addition to 5), the patient's guardian has sufficient understanding and written consent is obtained.

The exclusion criteria are as follows.
Patients whose postoperative follow-up period can be expected to be less than 6 months
Patients with edema due to heart failure, renal failure, etc.
Cases judged inappropriate by the investigator

The included patients were randomly assigned to the LVA group or the CDT group (assignment method is described below).

Adverse events

Adverse event
No adverse events were observed in the LVA group. Four patients in the CDT group had contact dermatitis due to compression garments, which improved with steroid ointment. A chi-square test showed that the incidence of adverse events was significantly higher in the CDT group

Outcome measures

Outcome
Evaluation was performed at the first outpatient visit after 6 months from the start of the intervention. In cases where it was difficult to see a doctor because the patient lived far away, a telephone interview was conducted after 6 months from the start of the intervention. The primary outcome was the frequency of cellulitis, recorded as the number of cellulitis episodes occurring over a 6-month period. Secondary outcomes included circumference measurements and stiffness measurements only in patients who visited the outpatient clinic after 6 months. Circumference was measured using a tape measure at six points: 20 cm proximal to the knee joint, 10 cm proximal to the knee joint, 10 cm distal to the knee joint, 10 cm distal to the knee joint, ankle joint, and dorsum of the foot. Measurements were taken during the afternoon outpatient visit and were randomly assigned to nurses or therapists. Hardness measurements were performed by the sponge method as previously reported [29]. Briefly, we prepared three types of sponges with different hardness (Yahata Neji Corp., Aichi, Japan). Each sponge was numbered 2, 4, or 6, with no. 2 as the softest. The sponges and recorded the number of the sponge that was most comparable in stiffness. The hardness was measured at a total of 8 points, dividing the thigh and lower leg into proximal/distal and medial/lateral regions, respectively.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2018

Year

02

Month

01

Day

Date of IRB

2018

Year

02

Month

01

Day

Anticipated trial start date

2018

Year

03

Month

01

Day

Last follow-up date

2020

Year

12

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

02

Month

24

Day

Last modified on

2022

Year

09

Month

24

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035913

Single case data URL

Value
https://center6.umin.ac.jp/ice/35913