Summary

for people ages 18 years and up (full criteria)
at La Jolla, California and other locations
study started
estimated completion:

Description

Summary

The purpose of this study is to determine if Extracorporeal Photopheresis (ECP) is effective in the treatment of progressive Bronchiolitis Obliterans Syndrome (BOS) in patients after lung transplantation. Lung transplantation has become the treatment of choice for selected patients with end-stage lung disease. However, long-term survival after transplantation remains disappointing. Chronic rejection (bronchiolitis obliterans syndrome [BOS]) has emerged as the leading obstacle to better long-term outcomes, and represents the leading cause of death beyond the first year after transplantation. BOS is diagnosed by the decline in the FEV1 measurement from a pulmonary function test. The management of BOS has been disappointing. In general, BOS is treated by intensifying the immunosuppressive regimen. Despite treatment, most patients continue to show progressive decline in lung function resulting in worsening functional status, quality of life, and ultimately graft failure and death. Extracorporeal Photopheresis (ECP) has been used as a salvage treatment for progressive BOS with favorable clinical results in many cases showing patient improvement. On May 2, 2012, the Center for Medicare Services issued a decision memo statin the ECP is covered for Medicare beneficiaries for the treatment of BOS following lung allograft transplantation only wehn the procedure is provided under a clinical research study. It is highly unlikely that providers that currently order ECP for their BOS patients who have already failed optimized immunosuppressive drug therapy would be willing to randomize half of their patients to continue on their failed drug therapy.What is not well understood at this time, however, is whether certain coexisting disease states or patient-related demographic, functional, treatment-related or diagnostic variables might prove to have predictive value in identifying subsets of BOS patients that are likely, or unlikely, to experience reduced rate of decline or stabilization in FEV1 following ECP treatment. This is a Registry study to enroll 160 patients from multiple U.S. centers to (1) confirm that ECP significantly reduces the rate of FEV1 decline in BOS patients refractory to standard immunosuppressive drug therapy, and (2) capture and assess specified patient demographic, treatment-related, diagnostic, functional and co-morbidity- related variables that may predict outcomes after ECP therapy.

Details

There is evidence to support that ECP benefits these patients, but we don't know how to predict which patients will benefit most. Patients will will be identified by physician investigators and co-investigators, and study staff, and through review of relevant administrative databases that are maintained for routine clinical care purposes (e.g. lung transplantation division database, pulmonary function laboratory database, etc.), subject to local IRB approval. Once eligibility is confirmed and the patient is provided informed consent, the patient will be assigned a unique case number created from the electronic data base. The patient demographics, co-morbidities, medical history including date of lung transplantation, underlying disease necessitating lung transplantation, vital signs, height , weight, and current medication regimen, maintenance immunosuppression and any changes in medication should be entered on the electronic case report forms. All FEV1 measurements captured within the 6 months prior to enrollment should be entered in the electronic case report forms.Certain source documents will be required and verified on all forms electronically submitted. Necessary source documents will be clearly requested on the electronic case report forms.

Patients should receive 24 ECP treatments over the 6-month period following enrollment, in accordance with the following schedule:

  • 8 to 10 treatments over the first 30 days following treatment initiation;
  • 8 to 10 treatments in the next 60 days (months 2 and 3);
  • 6 treatments in the next 90 days (months 4 through 6) at a rate of 2 treatments per month.

During ECP, blood is taken from the body through a standard venous catheter and the cells are separated by centrifugation via a specialized pheresis machine. The machine treats the blood with an agent called methoxsalen that becomes active when exposed to an ultraviolet light inside the machine. This changes the white blood cells to better enable them to reduce rejection and better suppress BOS. The machine then returns the blood into the patient through the catheter. .

An improvement in the FEV1 measurement taken from the pulmonary function test will be used to assess the success or the benefit of the ECP treatment. Patient's will have spirometry the first week of therapy, Day 30, 60, 90, 120, 150, 180, 240, 300, and at one year.

Statistical Methods -Based on a 95% power analysis and assuming a 5% loss to follow-up of enrolled patients, 160 patients will need to be enrolled to detect at least a 50% reduction in the rate of FEV1 decline at one-year follow-up. A 50% decrease in the rate of FEV1 decline can importantly extend survival and improve the opportunity to receive a new lung allograft, as well as delay time to onset of severe physical limitations. Our power analysis was based on findings from our previously published 60 patient series. Specifically, we first calculated values that reflected the difference between pre-intervention and post-intervention FEV1 slope values. The corresponding values for standard deviation of slope differences were adjusted for possible greater variability in the post-treatment period in this study. These values for derived slope differences (50% of 87 ml/month) and corresponding standard deviation values (150) were then used to calculate required enrollment using a treatment effect of 50% reduction of FEV1 decline and using a power of 95%. This analysis, with 5% late loss, indicates a required enrollment of 160 patients.

Keywords

Bronchiolitis Obliterans Syndrome (BOS) Bronchiolitis Obliterans Syndrome Lung Transplantation Extracorporeal Photopheresis Methoxsalen Syndrome Bronchiolitis Bronchiolitis Obliterans

Eligibility

You can join if…

Open to people ages 18 years and up

  • Adult age (at least 18 years old).
  • Medicare-eligible status
  • Lung transplant recipient (combined organ transplant recipients, e.g. heart- lung liver-lung recipients, are eligible).
  • Progressive BOS (defined as ongoing decline in FEV1 despite at least one of the following treatments; azithromycin, high-dose steroid, anti-thymocyte globulin, total lymphoid irradiation, sirolimus, or everolimus).
  • At minimum four FEV1 measurements obtained at intervals of one to six weeks apart,over the 6 months preceding initial ECP treatment (may include an FEV1 measurement on or just prior to the first ECP procedure date).

You CAN'T join if...

  • Participation in another clinical treatment trial with an investigational agent.
  • Any condition that may interfere with the subject's ability to perform pulmonary function testing.
  • Known allergy or hypersensitivity to pharmacologic agents used during ECP.
  • Any condition that would significantly affect the participant's ability to adhere to the protocol, affect interpretation of the study results, or put the participant at unacceptable risk for study-related complications as judged by the referring clinician. This may include patients with specific acute contraindication to receiving ECP due to any acute condition such as new or evolving myocardial infarction or central nervous system disorder, hemodynamic instability or hypovolemia, acute bleeding, or respiratory distress.
  • Inability to provide informed consent or to comply with study treatments or assessments (e.g. due to cognitive impairment or geographic distance).

Locations

  • University of California San Diego
    La Jolla California 92093 United States
  • University of Minnesota Medical Center, Fairview
    Minneapolis Minnesota 55455 United States
  • University of Iowa
    Iowa City Iowa 52242 United States
  • Washington University School of Medicine
    Saint Louis Missouri 63110 United States
  • University of Alabama at Birmingham
    Birmingham Alabama 35226 United States
  • Indiana University Health
    Indianapolis Indiana 46202 United States
  • University of Michigan Health System
    Ann Arbor Michigan 48109 United States
  • The Cleveland Clinic
    Cleveland Ohio 44195 United States
  • University of Pittsburgh
    Pittsburgh Pennsylvania 15213 United States
  • Columbia University
    New York New York 10032 United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Washington University School of Medicine
ID
NCT02181257
Study Type
Observational [Patient Registry]
Last Updated
December 15, 2017