UMIN-CTR Clinical Trial

Public title

Open uncontrolled investigation to evaluate the efficacy and safety of the granulocytes/ monocytes apheresis with the Adacolumn for the treatment of severe alcoholic hepatitis

Acronym

Study for the treatment of severe alcoholic hepatitis with granulocytes/ monocytes apheresis

Scientific Title

Open uncontrolled investigation to evaluate the efficacy and safety of the granulocytes/ monocytes apheresis with the Adacolumn for the treatment of severe alcoholic hepatitis

Scientific Title:Acronym

Study for the treatment of severe alcoholic hepatitis with granulocytes/ monocytes apheresis

Region

Japan

Condition

severe alcoholic hepatitis

Classification by specialty

Hepato-biliary-pancreatic medicine

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

severe alcoholic hepatitis (SAH) is life-threatening liver disease with jaundice that generally occurs after decades of large amount of alcohol use. The diagnosis of SAH is usually made based upon the Japanese SAH diagnostic criteria (Takada et al, J.Gastroenterol.Hepatol. 1995) as it follows; (1) alcoholic hepatitis with many alcoholic hyaline bodies, neutrophil infiltration and severe hepatic cell necrosis, (2) prothrombin activity (time) is less than 50%, and leukocytosis is prominent, (3) at high risk of death due to multiple organ failure (e.g. encephalopathy, acute renal failure and / or pneumonia, etc) within a month (4) endotoxemia is common; and (5) liver size does not decrease despite abstinence. Most SAH patients often have elevated and activated neutrophils. Typically, such patients have very poor prognosis (Horie, et al., Alcohol Clin Exp Res, 2005).
Corticosteroids are main stream of treatment for SAH in European and north American countries. Recently, it was reported that depleting elevated neutrophils by granulocytes / monocytes apheresis (GMA) can be alternative therapeutic option for patients with SAH having high neutrophil counts (Horie, et al., Alcohol Clin Exp Res, 2005). Adacolumn, a medical devise for the GMA, has been approved for the treatment of inflammatory bowel disease; ulcerative colitis and Crohn's disease, but not for SAH in Japan.
This single open labeled trial is aimed to evaluate the efficacy and safety of GMA with the Adacolumn for the treatment of SAH with elevated neutrophils. Eligible patients will receive GMA at 2 sessions per week for at least 2 weeks.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II

Primary outcomes

Survival rate at 90-days

Key secondary outcomes

The improvement rate of laboratory tests such as WBC, serum total bilirubin or prothrombin time, radiographic exam and pro-inflammatory cytokines/ chemokines.
The safety will be also assessed.

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Device,equipment

Interventions/Control_1

SAH patients receive GMA with Adacolumn, at 2 sessions per week for 2 weeks and more until WBC improves.
Laboratory examinations (WBC, PT, TB, etc.) and serum cytokines (IL-8, TNF-a, IL-6, ICAM-1) are monitored at baseline, 2 weeks after the first session and the end of a course of GMA therapy. Radiographic examination such as CT scan and liver biopsy are considered before and after GMA therapy if it is possible.

Interventions/Control_2

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

20

years-old

<=

Age-upper limit

70

years-old

>

Gender

Male and Female

Key inclusion criteria

This study includes patients
-with SAH diagnosed according to Japanese SAH diagnostic criteria
-with elevated neutrophil count (WBC>= 10000/mcL)
-with adequate peripheral blood access
-hospitalized,
-and obtained written informed consent from all patients or their family.

Key exclusion criteria

Patients with granulocyte <=2000/mcL.
Patients with severe infection.
Patients with severe heart disease.
Patients with hypotension (systolic pressure <=80mmHg).
Patients with pregnancy or planning to become pregnant.
Patients with malignant disease.
Patients with severe cirrhosis.
Patients with impossible to be quiet during GMA session even with the use of sedatives.

Target sample size

20

Name of lead principal investigator

1st name
Middle name
Last name	Toshifumi Hibi

Organization

Keio University

Division name

School of Medicine, Division of Gastroenterology & Hepatology, Department of Internal Medicine

Zip code

Address

35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan

TEL

03-3353-1211

Email

Name of contact person

1st name
Middle name
Last name	Yoshiyuki Yamagishi

Organization

Keio UniversityKeio University

Division name

School of Medicine, Division of Gastroenterology & Hepatology, Department of Internal Medicine

Zip code

Address

35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan

TEL

03-3353-1211

Homepage URL

Email

yyama@a8.keio.jp

Institute

Division of Gastroenterology & Hepatology, Department of Internal Medicine, School of Medicine, Keio University

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

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

慶應義塾大学病院（東京都）

Date of disclosure of the study information

2012

Year

08

Month

20

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

2010

Year

10

Month

20

Day

Date of IRB

Anticipated trial start date

2010

Year

10

Month

20

Day

Last follow-up date

Date of closure to data entry

2014

Year

12

Month

31

Day

Date trial data considered complete

2015

Year

03

Month

31

Day

Date analysis concluded

Other related information

Registered date

2012

Year

08

Month

08

Day

Last modified on

2013

Year

02

Month

12

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000010156