The Effect of Oxygen on Healing an Artery From the "Injury" of Surgery

May 23, 2012 updated by: University of Minnesota

Artery Wall Hypoxia and Intimal Hyperplasia

Many grafts placed for dialysis access fail which causes patients to undergo additional operations, decreases their quality of life, and increases health care costs. The purpose of this study is to see if dialysis access grafts will function longer for patients who receive additional oxygen by means of a nasal cannula for 42 days after placement of their graft.

Patients will have periodic blood tests to measure oxygen levels in their blood. A series of ultrasound examinations of patient's dialysis grafts will be taken to ensure the graft is open and to measure the cellular proliferation (intimal hyperplasia) for comparison in those receiving extra oxygen and those with no oxygen.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Vascular bypass grafting is a commonly performed procedure in vascular and cardiovascular surgery and the preferred bypass grafts are autogenous vein. Creation of a vascular anastomosis (AVA) is required at 2 sites (proximal and distal anastomoses) for every synthetic bypass graft. It is estimated that 50% of vascular bypass failures are due to anastomotic intimal hyperplasia (AIH). Intimal thickening of the artery wall is a normal response to healing at an anastomosis. Progression of intimal thickening leads to a pathological, hyperplastic, occlusive lesion - AIH, which in turn results in myocardial infarction, stroke, limb loss, death, graft failure, repeat operative procedures, and increased medical costs.

Our laboratory demonstrated in a rabbit model of AIH that: 1) there is a significant decrease in the delivery of oxygen to the peri-anastomotic artery wall following creation of a prosthetic vascular graft to artery anastomosis, 2) the oxygen gradient across the artery wall in the area of a prosthetic vascular graft anastomosis normalizes over a period of 6 weeks as healing occurs, 3) the gradient can be normalized immediately following an anastomosis by the administration of supplemental oxygen, and 4) the amount of AIH and smooth muscle cell proliferation can be reduced by immediately administering supplemental oxygen following creation of the anastomosis.

The long-range goal of our program is to understand the role of oxygen in blood vessel wall pathology. The specific objective of this project, which is the next step in the pursuit of our long-range program goal, is to determine if supplemental oxygen can inhibit AIH in a human graft model.

METHODS: Following review of inclusion and exclusion criteria suitable patients undergo surgical placement of a graft for hemodialysis. Following surgery, patients randomized to oxygen will breathe 5L supplemental oxygen during waking hours for 42 days. Periodic ultrasounds will be taken to assess graft function and patency and to measure intimal thickness. Patients will be followed for two years or until their graft fails.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55401
        • Abbott Northwestern Hospital
      • Minneapolis, Minnesota, United States, 55417
        • Veterans Affairs Medical Center
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota, Division of Vascular Surgery

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 18-80+/- referred and considered a candidate for a synthetic hemodialysis access graft.
  2. Baseline room air arterial blood concentration >70 and arterial carbon dioxide concentration 45 mmHg. Pulmonary function tests > 75% predicted values
  3. Currently undergoing dialysis
  4. No previous synthetic hemodialysis grafts placed in the same arm (fistula in ipsilateral arm permitted)
  5. Ability to use 5L/minute supplemental oxygen by nasal cannula
  6. Nonsmoker, able to avoid other situations which would constitute a risk for use of oxygen
  7. Medical condition with > 1 year life expectancy
  8. Currently on no medications which would interfere with wound healing (i.e. steroids, chemotherapeutic agents)
  9. Not pregnant nor planning to become pregnant during study period

Exclusion Criteria:

  1. Failure to meet inclusion criteria
  2. Failure to comply with study protocol for 3 consecutive days during the 6 wk oxygen/non-oxygen supplement period immediately following graft placement
  3. Medical condition developing during study period causing a significantly worsening pulmonary function requiring supplemental oxygen for > 3 days
  4. Need to take medication during study period which would interfere with wound healing any time during the 6 week period immediately following graft placement or need to take chronic medications (> 6 weeks) during the remainder of the study period.
  5. Patient desire to withdraw
  6. Failure of evidence of adequate increase in arterial blood oxygen concentration (pa02 > 115 for oxygen supplemented and pa02 > 55 mmHg for control obtained from arterial access port during dialysis run
  7. Failure to use supplemental oxygen (if in supplemental oxygen group) at least 18 hours per day (as recorded in journal) -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: 1
No exposure to supplemental oxygen
Other: Oxygen, treatment, supplement
6 weeks of supplemental oxygen delivered by nasal cannula post hemodialysis graft placement
Other: oxygen
5 Liter/minute by nasal cannula for 6 wks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The effect of supplemental oxygen on intimal thickness at the site of a hemodialysis access graft
Time Frame: Assessing intimal thickness in the first 2 yrs after graft placement
Assessing intimal thickness in the first 2 yrs after graft placement

Secondary Outcome Measures

Outcome Measure
Time Frame
Compare graft patency in oxygen supplemented vs. non oxygen supplemented group
Time Frame: Assessing graft patency in the first two years after graft placement
Assessing graft patency in the first two years after graft placement

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Minnesota

Investigators

  • Principal Investigator: Steven M Santilli, MD, PhD, MBA, University of Minnesota

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

August 1, 2009

Study Registration Dates

First Submitted

March 16, 2009

First Submitted That Met QC Criteria

March 16, 2009

First Posted (Estimate)

March 18, 2009

Study Record Updates

Last Update Posted (Estimate)

May 25, 2012

Last Update Submitted That Met QC Criteria

May 23, 2012

Last Verified

May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0010M69621
  • R01HL076316 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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