Oxaliplatin-induced Portal Hypertension

Construction and Evaluation of the Early Identification and Individualized Treatment for Oxaliplatin-induced Portal Hypertension

Oxaliplatin has been used as the first choice for the adjuvant chemotherapy of colorectal cancer and it has significantly improved the outcomes in patients with colorectal cancer. However, hepatotoxicity is the potentially problematic adverse effect of oxaliplatin. The pathological evaluation of non-tumoral liver from patients with advanced colorectal cancer undergoing neoadjuvant oxaliplatin-based treatment has provided histological evidence of hepatic sinusoidal injury. Oxaliplatin-induced sinusoidal injury can persist for more than 1 year after the completion of chemotherapy, and the increase in splenic volume may be a predictor of irreversible sinusoidal damage. In this current study, we aim to evaluate the efficacy of individualized treatment in patients with oxaliplatin-induced gastroesophageal varices after colorectal cancer surgery.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer; Gastroesophageal Varices Hemorrhage; Received Oxaliplatin-based Chemotherapy
• Intervention / Treatment: Procedure: Individualized Treatment

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Department of gastroenterology and hepatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Sign written informed consent
• Male or female patients aged 18-75
• diagnosed as portal hypertension by contrast-enhanced computed tomography
• and confirmed gastroesophageal varices by upper digestive endoscopy;
• had a history of oxaliplatin-based chemotherapy after colorectal cancer surgery;

Exclusion Criteria:

• combined known etiologies of chronic liver disease, including hepatitis, primary biliary cirrhosis, schistosomiasis, and non-alcoholic fatty liver disease.
• with colorectal cancer required further anti-tumor treatment
• Other factors judged by the investigator that may affect the safety of the subject or the compliance of the trial. Such as serious illnesses (including mental illness) that require combined treatment, serious laboratory abnormalities, or other family or social factors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Individualized Treatment Group	Procedure: Individualized Treatment; Patients under evaluation including hepatic venous pressure gradient (HVPG) and contrast-enhanced computed tomography of portal venous. For those patients with a HVPG ≥12mmHg or with extraluminal para-gastric vein will under transjugular intrahepatic portosystemic shunt and others receive endoscopic treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year rebleeding rate	1-year rebleeding rate	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year death rate	1-year death rate	1 year
Complications of portal hypertension	The occurrence of complications of portal hypertension including ascites, liver failure, et al.	1 year

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Publications and helpful links

General Publications

• Huang X, Li F, Wang L, Xiao M, Ni L, Jiang S, Ji Y, Zhang C, Zhang W, Wang J, Chen S. Endoscopic treatment of gastroesophageal variceal bleeding after oxaliplatin-based chemotherapy in patients with colorectal cancer. Endoscopy. 2020 Sep;52(9):727-735. doi: 10.1055/a-1157-8611. Epub 2020 May 7.
• Aloia T, Sebagh M, Plasse M, Karam V, Levi F, Giacchetti S, Azoulay D, Bismuth H, Castaing D, Adam R. Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases. J Clin Oncol. 2006 Nov 1;24(31):4983-90. doi: 10.1200/JCO.2006.05.8156.
• Iwai T, Yamada T, Koizumi M, Shinji S, Yokoyama Y, Takahashi G, Takeda K, Hara K, Ohta K, Uchida E. Oxaliplatin-induced increase in splenic volume; irreversible change after adjuvant FOLFOX. J Surg Oncol. 2017 Dec;116(7):947-953. doi: 10.1002/jso.24756. Epub 2017 Sep 6.
• Ward J, Guthrie JA, Sheridan MB, Boyes S, Smith JT, Wilson D, Wyatt JI, Treanor D, Robinson PJ. Sinusoidal obstructive syndrome diagnosed with superparamagnetic iron oxide-enhanced magnetic resonance imaging in patients with chemotherapy-treated colorectal liver metastases. J Clin Oncol. 2008 Sep 10;26(26):4304-10. doi: 10.1200/JCO.2008.16.1893.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 31, 2020
• Primary Completion (ANTICIPATED): October 31, 2021
• Study Completion (ANTICIPATED): September 30, 2022

Study Registration Dates

• First Submitted: August 20, 2020
• First Submitted That Met QC Criteria: August 20, 2020
• First Posted (ACTUAL): August 24, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 24, 2020
• Last Update Submitted That Met QC Criteria: August 20, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: oxaliplatin; portal hypertension; splenomegaly; colorectal carcinoma; gastroesophageal variceal bleeding
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Liver Diseases; Hypertension; Hemorrhage; Hypertension, Portal
• Other Study ID Numbers: PLAEGV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No