## Protocol Section
### Identification Module
**NCT ID:** NCT01499979

**Brief Title:** Hypothermic Perfusion During Hemihepatectomy

**Official Title:** In Situ Hypothermic Perfusion During Right Hemihepatectomy

#### Organization Study ID Info
**ID:** 2011_214
#### Organization
**Class:** OTHER
**Full Name:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
#### Secondary ID Infos
**Domain:** Centrale Commissie Mensgebonden Onderzoek (CCMO)
**ID:** NL37241.018.11
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2015-08

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2016-01-26

**Type:** ESTIMATED

**Last Update Submit Date:** 2016-01-25

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2015-05

**Type:** ACTUAL

#### Start Date
**Date:** 2012-02

**Status Verified Date:** 2016-01

#### Study First Post Date
**Date:** 2011-12-26
**Type:** ESTIMATED
**Study First Submit Date:** 2011-12-20
**Study First Submit QC Date:** 2011-12-23
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

#### Responsible Party

**Investigator Affiliation:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

**Investigator Full Name:** Megan J. Reiniers

**Investigator Title:** PhD student

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Rationale

Currently, hepatic resection is often the only curative treatment for primary or secondary hepatic malignancies and is also frequently performed in patients with benign liver tumors to prevent malignant transformation and/or alleviate symptoms. Liver resections are nowadays associated with low mortality and acceptable morbidity. As result of that, an increasing number of patients is currently under consideration for resection of more complex or large tumors, thus requiring extensive resection procedures. Application of vascular exclusion (i.e., clamping of the portal vein and hepatic artery) during such procedures reduces blood loss, which is one of the most important factors affecting peri-operative outcomes. However, vascular exclusion leads to ischemia-reperfusion (I/R) injury as an inevitable side-effect, which adversely impacts postoperative liver function and regeneration. Additional cooling of the liver by means of hypothermic perfusion is expected to further reduce intraoperative blood loss, as well as to protect the liver from I/R injury. Therefore, the aim of this pilot study is to cool the future remnant liver (FRL) in situ during right hemihepatectomy under vascular exclusion. Consequently, an overall improvement in postoperative outcomes is expected due to a decrease in intraoperative blood loss, reduced parenchymal damage, and a better ability of the liver remnant to regenerate.

Objective

To reduce intraoperative blood loss and enhance tolerance of the FRL to I/R injury during right hemihepatectomy under vascular exclusion by means of in situ hypothermic perfusion with retrograde outflow (R-IHP) of the FRL.

Study design

The study is designed as a prospective randomized pilot study in 18 patients (9 interventions and 9 controls) to assess the effects of the proposed intervention. Additionally, 4 patients will be included separately for assessment of the intervention's feasibility prior to randomized inclusion.

Study population

Eligible patients for participation in this study are those planned to undergo right hemihepatectomy under vascular inflow occlusion because of a malignant or benign liver tumor, and who do not suffer from any hepatic co-morbidity that might influence postoperative outcomes (i.e., severe steatosis, cholestasis, cirrhosis, or hepatitis B/C infection).

Intervention

During right hemihepatectomy, the FRL of patients allocated to the intervention group will be perfused with a chilled perfusion solution (i.e., lactated Ringer's solution).

### Conditions Module

**Conditions:**

- Hepatic Ischemia-reperfusion Injury

**Keywords:**

- Ischemia-reperfusion injury

- In situ hypothermic perfusion

- In situ hypothermic preservation

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** SINGLE

**Who Masked:**

- PARTICIPANT

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 22

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients that will receive intermittent vascular inflow occlusion, the standard method for vascular occlusion at our institution, during liver resection.

**Label:** Vascular inflow occlusion

**Type:** NO_INTERVENTION

#### Arm Group 2

**Description:** Patients will receive in situ hypothermic perfusion of the future remnant liver during liver resection.

**Intervention Names:**

- Procedure: In situ hypothermic perfusion

**Label:** Hypothermic perfusion

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Hypothermic perfusion

**Description:** In situ perfusion of the future remnant liver with chilled lactated Ringer's solution during liver resection.

**Name:** In situ hypothermic perfusion

**Other Names:**

- In situ hypothermic preservation

**Type:** PROCEDURE

### Outcomes Module

#### Primary Outcomes

**Description:** Hepatocellular damage expressed as an postoperative increase in transaminases (i.e., AST and ALT).

**Measure:** Postoperative hepatocellular damage

**Time Frame:** 5 days postoperatively

#### Secondary Outcomes

**Description:** Blood loss during surgery

**Measure:** Intraoperative blood loss

**Time Frame:** 2-3 hours

**Description:** Incidence of surgery-related complications

**Measure:** Postoperative complications

**Time Frame:** 5 days postoperatively

**Description:** Regeneration of liver function (measured via hepatobiliary scintigraphy) and -volume (measured via CT volumetry).

**Measure:** Regeneration of liver function and volume

**Time Frame:** 3 days

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Patients scheduled for right hemihepatectomy under vascular inflow occlusion for a malignant or benign hepatic tumor
* Diagnostic exclusion of hepatic co-morbidity, that is:

  * Cirrhosis,
  * Severe steatosis (≥ 30%),
  * Cholestasis, and
  * Hepatitis B/C infection
* Age ≥ 18 years
* Signed informed consent obtained prior to any study-specific procedure
* ASA classification I-III

Exclusion Criteria:

* Patients diagnosed with any of the hepatic co-morbidities listed under point 2 of the inclusion criteria
* Age \< 18 years
* BMI \> 35 kg/m2
* ASA classification IV/V
* Patient is scheduled for a combined surgical procedure (e.g., bile duct resection, gastrointestinal procedures)
* Patient underwent liver resection ≤ 1 year prior to scheduled surgery
* Emergency operations
* Pregnancy or breast feeding

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Amsterdam

**Country:** Netherlands

**Facility:** Academic Medical Center (AMC)

**State:** Noord-Holland

**Zip:** 1105 AZ

#### Overall Officials

**Official 1:**

**Affiliation:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

**Name:** Prof. Thomas M. van Gulik, MD, PhD

**Role:** STUDY_CHAIR

**Official 2:**

**Affiliation:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

**Name:** Megan J. Reiniers, MSc

**Role:** PRINCIPAL_INVESTIGATOR

**Official 3:**

**Affiliation:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

**Name:** Rowan F. van Golen, MSc

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

### References Module

#### References

**Citation:** Azoulay D, Eshkenazy R, Andreani P, Castaing D, Adam R, Ichai P, Naili S, Vinet E, Saliba F, Lemoine A, Gillon MC, Bismuth H. In situ hypothermic perfusion of the liver versus standard total vascular exclusion for complex liver resection. Ann Surg. 2005 Feb;241(2):277-85. doi: 10.1097/01.sla.0000152017.62778.2f.

**PMID:** 15650638

**Citation:** Dinant S, van Veen SQ, Roseboom HJ, van Vliet AK, van Gulik TM. Liver protection by hypothermic perfusion at different temperatures during total vascular exclusion. Liver Int. 2006 May;26(4):486-93. doi: 10.1111/j.1478-3231.2006.01248.x.

**PMID:** 16629653

**Citation:** Verhoef C, de Wilt JH, Brunstein F, Marinelli AW, van Etten B, Vermaas M, Guetens G, de Boeck G, de Bruijn EA, Eggermont AM. Isolated hypoxic hepatic perfusion with retrograde outflow in patients with irresectable liver metastases; a new simplified technique in isolated hepatic perfusion. Ann Surg Oncol. 2008 May;15(5):1367-74. doi: 10.1245/s10434-007-9714-z. Epub 2008 Feb 1.

**PMID:** 18239976

**Citation:** Reiniers MJ, van Golen RF, Heger M, Mearadji B, Bennink RJ, Verheij J, van Gulik TM. In situ hypothermic perfusion with retrograde outflow during right hemihepatectomy: first experiences with a new technique. J Am Coll Surg. 2014 Jan;218(1):e7-16. doi: 10.1016/j.jamcollsurg.2013.09.013. Epub 2013 Nov 6. No abstract available.

**PMID:** 24210146

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000011183

- Term: Postoperative Complications

- ID: D000001832

- Term: Body Temperature Changes

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC14

- Name: Heart and Blood Diseases

### Condition Browse Module - Browse Leaves

- ID: M10085

- Name: Hypothermia

- Relevance: HIGH

- As Found: Hypothermic

- ID: M10543

- Name: Ischemia

- Relevance: HIGH

- As Found: Ischemia

- ID: M18099

- Name: Reperfusion Injury

- Relevance: HIGH

- As Found: Reperfusion Injury

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14065

- Name: Postoperative Complications

- Relevance: LOW

- As Found: Unknown

- ID: M5111

- Name: Body Temperature Changes

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000015427

- Term: Reperfusion Injury

- ID: D000007511

- Term: Ischemia

- ID: D000007035

- Term: Hypothermia

### Intervention Browse Module - Browse Branches

- Abbrev: PhSol

- Name: Pharmaceutical Solutions

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Hemat

- Name: Hematinics

### Intervention Browse Module - Browse Leaves

- ID: M21860

- Name: Pharmaceutical Solutions

- Relevance: LOW

- As Found: Unknown

- ID: M11110

- Name: Liver Extracts

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
