Pancreaticoduodenectomy With or Without Preoperative Hyperbaric Oxygen Therapy

Duodenal Neoplasms Clinical Trial

— HBOT  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02575014
• Other study ID #: HBOT 529762
• Status: Enrolling by invitation
• Phase: N/A
• First received: October 7, 2015
• Last updated: February 6, 2018
• Start date: October 2013
• Est. completion date: December 2022

Study information

• Verified date: February 2018
• Source: Florida Hospital Tampa Bay Division
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 50
• Est. completion date: December 2022
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bile Duct Neoplasms
• Common Bile Duct Neoplasms
• Duodenal Neoplasms
• Neoplasms
• Periampullary Tumor

Intervention

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.

Locations

Country	Name	City	State
United States	Florida Hospital Tampa	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Florida Hospital Tampa Bay Division

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Death		Postoperative up to 5 years
Secondary	Length of hospital stay		Postoperative up to one month
Secondary	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
Secondary	Change in Interleukin-2		Postoperative up to one month
Secondary	Change in Interleukin-6		Postoperative up to one month
Secondary	Change in Interleukin-10		Postoperative up to one month
Secondary	Change in Vascular Endothelial Growth Factor		Postoperative up to one month
Secondary	Change in Transforming Growth Factor-Beta		Postoperative up to one month
Secondary	Change in Erythrocyte Sedimentation Rate		Postoperative up to one month
Secondary	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
Secondary	Change in pain score according to visual analog scale	Postoperative pain will be compared to preoperative pain	Postoperative up to one month
Secondary	Change in Cancer Antigen 19-9		Postoperative up to one year
Secondary	Change in Carcinoembryonic antigen		Postoperative up to one year