Pancreaticoduodenectomy With or Without Preoperative Hyperbaric Oxygen Therapy (HBOT)

Preoperative Hyperbaric Oxygen Therapy (HBOT) vs. Non Preoperative HBOT in Patients Undergoing Pancreaticoduodenectomy for Premalignant, and Malignant Tumors of the Common Bile Duct, Periampullary and Duodenum

The primary objective of this study is to assess the safety, tolerability and toxicity of preoperative HBOT in patients undergoing a pancreaticoduodenal resection for premalignant and malignant tumors of the common bile duct, periampullary and duodenum.

Study Overview

• Status: Unknown
• Conditions: Duodenal Neoplasms; Periampullary Tumor; Common Bile Duct Neoplasms
• Intervention / Treatment: Drug: Preoperative hyperbaric oxygen

Detailed Description

Patients diagnosed with premalignant and malignant tumors of the common bile duct, periampullary and duodenum will be screened for eligibility within 4 weeks of their scheduled surgery. Initiation of therapy is defined as the first day of HBOT for patients receiving HBOT therapy (Arm A) and the day of surgery for patients not receiving HBOT (Arm B). Patients will be considered "enrolled into study" once the consent form has been signed, all screening procedures have been undertaken and all the eligibility criteria are met. The fifty eligible patients will be randomized in a 1:1 ratio the same day of the screening process. The eligible subjects undergoing HBOT will be treated with up to 2.4 Atmospheres Absolute (ATA) of oxygen (O2), for a maximum of 90 minutes each day with or without air breaks, as deemed necessary by the investigator, for two days. Patients who are deemed ineligible will receive the same standard of care without any exceptions. The start day of the week to commence HBOT will be Monday through Wednesday, as the second and final day of HBOT treatment will be the day in which the patient undergoes pancreaticoduodenectomy. The subjects who complete the HBOT regimen must undergo subsequent pancreaticoduodenectomy within five hours of termination of HBOT. If there is more than a five hour delay from completion of the HBOT to commencement of operation, the subject will be considered "off study treatment". However, "off study treatment" patients will continue to be followed up every six months for the first thirty months, and annually thereafter. During the postoperative period, clinical data and questionnaire forms will be collected on day 1, day 3, day 5, and one month (± 2 weeks) during the first year. As for secondary objectives, the investigators will collect clinical data from patients during their follow up visits in the office, by contacting them on the phone, or by mailing them the protocol specific questionnaires every 6 months for 5 years.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33613
      • Florida Hospital Tampa

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• All patients diagnosed via endoscopic ultrasound (EUS) and fine needle aspiration (FNA) or CT-guided biopsy with periampullary adenocarcinoma, duodenal cancer, premalignant lesions of the pancreas (pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm) and cholangiocarcinoma (Klatskin tumor) undergoing pancreaticoduodenectomy
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2
• One or more comorbidities:

Diabetes Mellitus Chronic Obstructive Pulmonary Disease Cardiac Disease: history of angina, myocardial infarction, previous percutaneous cardiac intervention, or cardiac surgery, dysrhythmia Peripheral Vascular Disease: history of revascularization or amputation, rest pain, or gangrene Neurological Disease: history of stroke with or without residual deficit, seizure disorder, transient ischemic attack, hemiplegia, paraplegia, or impaired sensorium Dyspnea Bleeding Disorder Metabolic Disease (e.g. BMI ≥ 35) Renal Insufficiency Hepatic Insufficiency Another comorbidity that in the opinion of the investigator makes the patient compromised

• Nutritionally depleted. Albumin level ≤ 3.5 grams/deciliter (g/dL)
• Adequate organ function defined as:

Absolute neutrophil count >1,500 / (microliter) mcL Platelets >100,000 / mcL Total bilirubin <2.5 time upper limits of normal Aspartate aminotransferase (AST) / Alanine transaminase (ALT) <2.5 times institutional upper limit of normal Creatinine within normal institutional limits OR creatinine clearance >60 mL/min/ per Cockcroft-Gault equation for patients with creatinine levels above institutional normal

- Signed informed consent

Exclusion Criteria:

• History of asthma. There is some evidence that the administration of some bronchodilators may increase the incidence of gas embolism to the brain through pulmonary vasodilation.
• Congenital spherocytosis. Increased risk of massive hemolysis.
• High grade fever at time of screening (more than 38.5 degree Celsius tend to lower the seizure threshold due to oxygen toxicity and may result in the delay of relatively routine therapy
• Optic neuritis.
• Upper respiratory tract infection and viral infection (relative contra-indications due to the difficulty such patients may have in clearing their ears and sinuses.
• Pregnancy.
• Emphysema with carbon dioxide retention.
• Viral infection. There are controversial clinical evidences whether the hyperbaric oxygen therapy (HBOT) can be helpful in eliminating viral infections or otherwise viral infections may be considerably worsened after HBOT.
• Cisplatin therapy (some evidence that this drug retards wound healing when combined with HBOT).
• Disulphiram therapy. Evidence suggests that this drug blocks the production of superoxide dismutase. This may severely affect the body's ability to neutralize oxygen free radicals.
• Doxorubicin therapy. This chemotherapeutic agent becomes increasingly toxic under pressure. Animal studies suggest at least a one-week break between last dose and first treatment of HBOT.
• Claustrophobia. Some degree of confinement anxiety has been reported.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Preoperative HBOT; 25 out of 50 patients will receive 2 preoperative hyperbaric oxygen therapy treatments, one the day before their operation, the other within 5 hours preceding their operation. The participants will be treated with up to 2.4 ATA O2, for a maximum of 90 minutes each day with or without air breaks, as deemed necessary by the investigator. Day 0 will be the first day of their HBOT treatment, Day 1 will be the day of their operation and second/final HBOT treatment.	Drug: Preoperative hyperbaric oxygen; Subjects undergoing preoperative HBOT will be treated with up to 2.4 ATA O2, for a maximum of 90 minutes each day with or without air breaks, as deemed necessary by the investigator, for two days. The two days will be the day of and the day immediately prior to the operation.; Other Names: O2
No Intervention: No HBOT; 25 out of 50 patients will not receive preoperative hyperbaric oxygen therapy. Day 1 will be the day of the operation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with hyperbaric oxygen treatment related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03	ear pain, oxygen toxicity, visual changes, embolism, pneumothorax, fatigue	Preoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death		Postoperative up to 5 years
Length of hospital stay		Postoperative up to one month
Postoperative complications	Surgical wound infections, hernia, abscess, fluid collection, bleeding, anastomotic leak, thromboembolic events, pulmonary atelectasis, bronchospasm, pneumonia, stroke, myocardial ischemia, myocardial infarction, time to extubation for patients requiring prolonged mechanical assistance, biliary or pancreatic fistula, fever, blood transfusion, delayed gastric emptying,	Postoperative up to one month
Change in Interleukin-2		Postoperative up to one month
Change in Interleukin-6		Postoperative up to one month
Change in Interleukin-10		Postoperative up to one month
Change in Vascular Endothelial Growth Factor		Postoperative up to one month
Change in Transforming Growth Factor-Beta		Postoperative up to one month
Change in Erythrocyte Sedimentation Rate		Postoperative up to one month
Change in Quality of Life QOL-C30 v1.0	Postoperative quality of life scores will be compared to preoperative quality of life	Postoperative up to 5 years
Change in pain score according to visual analog scale	Postoperative pain will be compared to preoperative pain	Postoperative up to one month
Change in Cancer Antigen 19-9		Postoperative up to one year
Change in Carcinoembryonic antigen		Postoperative up to one year

Collaborators and Investigators

• Sponsor: Florida Hospital Tampa Bay Division
• Investigators: Principal Investigator: Alexander S Rosemurgy, MD, Florida Hospital Tampa

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: October 7, 2015
• First Submitted That Met QC Criteria: October 12, 2015
• First Posted (Estimate): October 14, 2015

Study Record Updates

• Last Update Posted (Actual): February 7, 2018
• Last Update Submitted That Met QC Criteria: February 6, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Duodenal Diseases; Biliary Tract Diseases; Bile Duct Diseases; Common Bile Duct Diseases; Biliary Tract Neoplasms; Neoplasms; Bile Duct Neoplasms; Duodenal Neoplasms; Common Bile Duct Neoplasms
• Other Study ID Numbers: HBOT 529762

Plan for Individual participant data (IPD)

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