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

This study has been terminated.
(Clinical changes: graft to fistula first; enrollment of 46/132 planned. NIH approved animal model: supplemental oxygen/AV fistula.)
Sponsor:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT00863603
First received: March 16, 2009
Last updated: May 23, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention
End Stage Renal Disease
Other: oxygen

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Artery Wall Hypoxia and Intimal Hyperplasia

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Compare graft patency in oxygen supplemented vs. non oxygen supplemented group [ Time Frame: Assessing graft patency in the first two years after graft placement ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: January 2005
Study Completion Date: August 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 1
No exposure to supplemental oxygen
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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) -
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00863603

Locations
United States, Minnesota
University of Minnesota, Division of Vascular Surgery
Minneapolis, Minnesota, United States, 55455
Abbott Northwestern Hospital
Minneapolis, Minnesota, United States, 55401
Veterans Affairs Medical Center
Minneapolis, Minnesota, United States, 55417
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Investigators
Principal Investigator: Steven M Santilli, MD, PhD, MBA University of Minnesota - Clinical and Translational Science Institute
  More Information

Publications:

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT00863603     History of Changes
Other Study ID Numbers: 0010M69621, RO1HL076316
Study First Received: March 16, 2009
Last Updated: May 23, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
Supplemental oxygen
Intimal hyperplasia
Graft patency

Additional relevant MeSH terms:
Hyperplasia
Kidney Diseases
Kidney Failure, Chronic
Pathologic Processes
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency

ClinicalTrials.gov processed this record on July 31, 2014