Combined Resection vs. Separated Resection After Mobilization of Splenic Vein During Distal Pancreatectomy (COSMOS-DP)

Comparison of Resection During Distal Pancreatectomy of the Splenic Vein Either Together With the Pancreatic Parenchyma or After Isolation: A Multicentre, Prospective, Randomized Phase III Trial

Eligible patients will be centrally randomized to either Arm A (resection of the splenic vein after isolation from the pancreatic parenchyma) or Arm B (co-resection of the vein together with the pancreas).

Study Overview

• Status: Unknown
• Conditions: Pancreatic Neoplasms
• Intervention / Treatment: Procedure: separated resection of the splenic vein; Procedure: combined resection of the splenic vein

Detailed Description

In distal pancreatectomy, it is customary to ligate and divide the splenic vein after isolating it from the pancreatic parenchyma. This is considered essential to prevent disruption of the stump of the splenic vein and the consequent intra-abdominal haemorrhage in the event of pancreatic fistula. This procedure can be technically demanding, especially when the vein is firmly embedded in the pancreatic parenchyma. The objective of this trial is to confirm the non-inferiority of resection of the splenic vein embedded in the pancreatic parenchyma compared with the conventional technique of isolating the splenic vein before resection during distal pancreatectomy using a mechanical stapler.

• Study Type: Interventional
• Enrollment (Anticipated): 304
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Wakayama, Japan, 641-8510
    • Recruiting
    • Wakayama Medical University
    • Contact: Hiroki Yamaue, MD, PhD; Phone Number: +81-73-441-0613; Email: yamaue-h@wakayama-med.ac.jp
    • Sub-Investigator: Tsutomu Fujii, MD, PhD
    • Sub-Investigator: Manabu Kawai, MD, PhD
    • Sub-Investigator: Suguru Yamada, MD, PhD
    • Sub-Investigator: Yuichi Nagakawa, MD, PhD
    • Sub-Investigator: Sohei Satoi, MD, PhD
    • Sub-Investigator: Hidetoshi Eguchi, MD, PhD
    • Sub-Investigator: Yoshiaki Murakami, MD, PhD
    • Sub-Investigator: Masafumi Nakamura, MD, PhD
    • Sub-Investigator: Toshio Shimokawa, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Elective open or laparoscopic distal pancreatectomy for diseases of the pancreatic body and tail
• ECOG Performance Status (PS) = 0-1
• Age ≥ 20 years old
• Maintenance of functioning of the major organs (bone marrow, liver, kidney, lung, etc.) (a) White blood cells ≥ 2,500/mm3 (b) Haemoglobin ≥ 9.0 g/dL (c) platelets ≥ 100,000/mm3 (d) Total bilirubin ≤ 2.0 mg/dL (e) Creatinine ≤ 2.0 mg/dL (v) Sufficient judgement to understand the study and to provide written informed consent

Exclusion Criteria:

• Splenic vein-preserving distal pancreatectomy
• Superior mesenteric vein or portal vein invasion
• Pancreatic trauma
• Preoperative inflammatory pancreatic disease (pancreatitis)
• Requirement of anti-coagulant treatment during or after surgery. Anti-coagulant treatment at 24 hrs after surgery is allowed.
• Severe ischemic cardiovascular disease
• Liver cirrhosis or active hepatitis
• Need for oxygen due to interstitial pneumonia or lung fibrosis
• Dialysis due to chronic renal failure
• Need for surrounding organ resection (stomach, colon, etc.), excluding the left adrenal gland and gall bladder
• Active multiple cancer that is thought to influence the occurrence of adverse events
• Difficulty with study participation due to psychotic disease or symptoms
• Inappropriate use of the stapler
• Inappropriate for the study objectives

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: separated resection of the splenic vein; separated resection of the splenic vein from the pancreatic parenchyma before ligation and division during distal pancreatectomy using mechanical staplers.	Procedure: separated resection of the splenic vein; separated resection of the splenic vein from the pancreatic parenchyma before ligation and division during distal pancreatectomy using mechanical staplers.
Experimental: combined resection of the splenic vein; combined resection of the splenic vein with the pancreatic parenchyma before ligation and division during distal pancreatectomy using mechanical staplers.	Procedure: combined resection of the splenic vein; combined resection of the splenic vein with the pancreatic parenchyma before ligation and division during distal pancreatectomy using mechanical staplers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the incidence of pancreatic fsitula grade B/C	6 months after operation

Secondary Outcome Measures

Outcome Measure	Time Frame
the incidence of pancreatic fsitula of all grades	6 months after operation
the incidence of pancreatic fsitula grade C	6 months after operation
the incidenceof intra-abdominal haemorrhage	6 months after operation
the incidence of all complications	6 months after operation
comparison of the thickness of the resected pancreatic parenchyma with the incidence of PF grade B/C	6 months after operation
mortality	6 months after operation
the incidence of thrombosis of the splenic vein	6 months after operation
the operative time	during operation
volume of blood loss	during operation
thickness of the resected pancreatic parenchyma	during operation
haemostasis of the staple line	during operation
integrity of the staple line	during operation
the incidence of pancreatic injury	during operation
need for additional sutures to securely close the pancreatic stump	during operation
time needed for pancreatic transection	during operation
duration of drainage tube placement	6 months after operation
postoperative hospital stay duration	6 months after operation
the incidence of conversion from laparoscopic surgery to open surgery	during operation

Collaborators and Investigators

• Sponsor: Wakayama Medical University
• Investigators: Principal Investigator: Hiroki Yamaue, MD, PhD, Wakayama Medical University

Publications and helpful links

General Publications

• Yamada S, Fujii T, Sonohara F, Kawai M, Shibuya K, Matsumoto I, Fukuzawa K, Baba H, Aoki T, Unno M, Satoi S, Kishi Y, Hatano E, Uemura K, Horiguchi A, Sho M, Takeda Y, Shimokawa T, Kodera Y, Yamaue H. Safety of Combined Division vs Separate Division of the Splenic Vein in Patients Undergoing Distal Pancreatectomy: A Noninferiority Randomized Clinical Trial. JAMA Surg. 2021 May 1;156(5):418-428. doi: 10.1001/jamasurg.2021.0108.
• Yamada S, Fujii T, Kawai M, Shimokawa T, Nakamura M, Murakami Y, Satoi S, Eguchi H, Nagakawa Y, Kodera Y, Yamaue H. Splenic vein resection together with the pancreatic parenchyma versus separated resection after isolation of the parenchyma during distal pancreatectomy (COSMOS-DP trial): study protocol for a randomised controlled trial. Trials. 2018 Jul 11;19(1):369. doi: 10.1186/s13063-018-2756-7.

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Anticipated): August 1, 2019
• Study Completion (Anticipated): February 1, 2020

Study Registration Dates

• First Submitted: July 27, 2016
• First Submitted That Met QC Criteria: August 15, 2016
• First Posted (Estimate): August 18, 2016

Study Record Updates

• Last Update Posted (Estimate): August 18, 2016
• Last Update Submitted That Met QC Criteria: August 15, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: COSMOS-DP trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No