Dexmedetomidine and HIPEC

NCT ID: NCT04106999

Last Updated: 2022-11-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-31
• Study Completion Date: 2024-12-31

Brief Summary

Inflammation is associated with an increased risk of cancer recurrence. Various methods have been used to decrease the inflammatory response induced by the cancer and surgery. In this study the investigators would like determine if a commonly used sedative drug (dexmedtomidine) has an impact on this inflammatory state when used as part of the anesthetic. The investigators will conduct a pilot study with 20 patients undergoing a Hyperthermic Intraperitoneal Chemotherapy (HIPEC) procedure as part of their cancer treatment. 10 patients will receive the standard of care for anesthesia during the cancer surgery and a placebo infusion of normal saline at a rate consistent to that of the study drug. 10 additional patients will receive the same standard of care anesthetic plan with the addition of an infusion of dexmeditomidine during the procedure. The investigators will measure the degree of inflammation before, during and after the surgical procedure by looking at the levels of inflammatory markers in blood samples. The goal is to determine if the addition of dexmodtomidine affects the inflammatory state of patients undergoing a HIPEC procedure. This information will be used to guide future studies aiming at decreasing cancer recurrence and improve patient outcomes.

Detailed Description

Purpose: To investigate the use of intra-operative dexmedetomidine infusions to reduce the inflammatory and stress response of cytoreductive treatment and hyperthermic intra-peritoneal chemotherapy (HIPEC).

Hypothesis: HIPEC surgery patients who receive an intra-operative infusion of dexmedetomidine in addition to the current standard of care, consisting of parenteral and enteral opioids and thoracic epidural will have a reduction in their inflammatory markers intra-operatively, in PACU, POD1 and POD5 and a reduction in oral morphine equivalent opioid consumption in PACU and POD1, in comparison to those who receive a placebo infusion.

Justification: Surgical tumor excision is a cornerstone of primary cancer treatment, but is also recognized as one of the greatest risk factors for metastatic spread. The perioperative period, characterized by the surgical stress response and pharmacologic-induced angiogenesis and immunomodulation, results in a physiologic environment that supports tumor spread and distant reimplantation. There is potential for anesthesiologists to modulate the unwanted consequences of the stress response on the immune system and minimize residual disease by altering their anesthetic plan.

Dexmedtomidine is a commonly used sedative that can be used as part of an anesthetic during surgery. In vitro and animal studies have shown that dexmedtomidine decreases the inflammatory response but no research has been conducted with cancer-related conditions.

Objective: To determine if dexmedtomidine, when used intraoperatively, can decrease the levels of inflammation in patients a Hyperthermic Intraperitoneal Chemotherapy (HIPEC) procedure as part of their cancer treatment.

Primary Objective:

Reduction in inflammatory markers: CRP, ESR, NLR, PLR, plasma viscosity, lactate.

Secondary Objectives Reduction in Cancer markers: CEA (carcinoembyronic antigen] and CA19-9 Reduction in opioid use Reduction in volatile usage (average sevoflurane end-tidal level)

Research Design: In this pilot study, 20 patients undergoing a HIPEC procedure as part of their cancer treatment will be randomized into 2 groups. One group (controls) will receive the current anesthetic standard of care. The second group (experimental) will also receive the current anesthetic standard of care with the addition of an infusion of dexmedtomidine during the surgical procedure. Biomarkers of inflammation (Lactate, CRP, ESR, plasma viscosity, NLR, PLR, and procalcitonin) and cancer markers (CEA and CA19-9) will be measured at 5 time points: pre-operatively, intra-opertatively prior to chemotherapy, post-operatively in the post-anaesthetic care unit, post-operative day 1, and post-operative day 5. Quantitative analysis of the inflammatory markers will be used to compare the two groups.

Statistical Analysis: Data will be summarized and t-tests will be used to compare the data from the 2 groups.

Conditions

Inflammation; Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Normal Saline will be infused as per the protocol

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

Normal Saline will be infused as a control drug

Intervention group

Dexmedetomidine will be infused as per the protocol

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: DRUG

Drug infusion will be delivered intra-operatively

Interventions

Dexmedetomidine

Drug infusion will be delivered intra-operatively

Intervention Type: DRUG

Placebos

Normal Saline will be infused as a control drug

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients undergoing a Hyperthermic Intraperitoneal Chemotherapy (HIPEC) procedure as part of their cancer treatment at Vancover General Hospital
• 18 years of age or older
• Able to provide informed consent
• Expected stay 5 days or greater in hospital
• Presenting for HIPEC with Colon or Appendix Cancer

Exclusion Criteria

• Contraindication to dexmedtomidine use including allergy or sensitivity to the drug
• Pregnancy
• Dementia
• ASA greater than or equal to 4
• Significant liver disease
• Current use of steroid or immunosuppressive medication
• Mesothelioma tumour origin
• Current use of clonidine
• Current opioid use exceeding 30mg of oral morphine equivalents
• Patient not eligible or patient refusal to have a thoracic epidural

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Jason Wilson

Clinical Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

UBC/Medicine, Faculty of/Anesthesiology, Pharmacology & Therapeutics

Vancouver, British Columbia, Canada

Countries

Canada

Other Identifiers

H19-00859

Identifier Type: -

Identifier Source: org_study_id