Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Extracorporeal Photopheresis for Medicare Recipients of Lung Allografts (ECP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02181257
Recruitment Status : Recruiting
First Posted : July 3, 2014
Last Update Posted : February 21, 2020
Sponsor:
Collaborators:
Centers for Medicare and Medicaid Services
Mallinckrodt
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
The primary aims of this study is to determine the efficacy and tolerability of Extracorporeal Photopheresis (ECP) for the treatment of either refractory (240) or newly diagnosed (739) Bronchiolitis Obliterans Syndrome (BOS) in patients after lung transplantation.In compliance with the Centers for Medicare and Medicaid Services' (CMS) Coverage with Evidence Development (CED) decision, the study will collect specified demographic, comorbidity, treatment, and outcome data exclusively for Medicare beneficiaries who are treated with Extracorporeal Photopheresis for either refractory or New Bronchiolitis Obliterans Syndrome .

Condition or disease Intervention/treatment Phase
Bronchiolitis Obliterans Syndrome (BOS) Combination Product: Extracorporeal Photopheresis (ECP) Phase 3

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 979 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: REFRACTORY BOS - Participants are electronically assigned to either ECP Treatment or OBSERVATION (Standard Immunosuppression Therapy) NEW BOS Participants are randomized to ECP Treatment or CONTROL (Standard Immunosuppression Therapy
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Extracorporeal Photopheresis for the Management of Progressive Bronchiolitis Obliterans Syndrome in Medicare-Eligible Recipients of Lung Allografts
Study Start Date : January 2015
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Medicare

Arm Intervention/treatment
Newly Diagnosed Bronchiolitis Obliterans

Participants with newly diagnosed Bronchiolitis Obliterans Syndrome will be randomized to Early Photopheresis Intervention or Control (Standard of Care). Participants randomized to Early Photopheresis Intervention will receive Extracorporeal Photopheresis Treatments. The patient has 24 treatments in a 6 month period and may continue maintenance treatments.

The Control group will receive local Standard of Care for the management of Bronchiolitis Obliterans Syndrome. Therapy will involve changes in immunosuppressive agents.

Combination Product: Extracorporeal Photopheresis (ECP)
Procedure Extracorporeal Photopheresis Treatments will be performed using one of twoTherakos systems. Both systems used the drug Methoxsalen

Refractory Bronchiolitis Obliterans
Participants with Refractory Bronchiolitis Obliterans Syndrome are electronically assigned to either Extracorporeal Photopheresis treatment or Observation based on the participant's Forced Expiratory Volume. Values from pulmonary function tests from the preceding 12 months will be entered into a web-based treatment allocation which will perform an automated calculation. Patients who have a statistically significant rate of decline within the preceding 6 months, and a derived protocol defined slope, will be assigned to the Extracorporeal Photopheresis Treatment Cohort. If a patient does not meet these criteria, the participant will be assigned to the Observation Cohort.
Combination Product: Extracorporeal Photopheresis (ECP)
Procedure Extracorporeal Photopheresis Treatments will be performed using one of twoTherakos systems. Both systems used the drug Methoxsalen




Primary Outcome Measures :
  1. Patients with Refractory Bronchiolitis Obliterans receiving Extracorporeal Photopheresis will have a 50% or greater reduction in the rate of decline of Forced Expiratory Volume before and after the treatment. [ Time Frame: 12 months following the initiation of ECP. ]
    For the REFRACTORY BOS -The study will prospectively capture Forced Expiratory Volume during the course of Extracorporeal photopheresis therapy every 30 days and out to one year, and then annually.

  2. Survival: 25% reduction in mortality [ Time Frame: Three years after randomization compared with patients in the Control ]
    Patients receiving Early Photopheresis Intervention will experience a 25% reduction in mortality three years after randomization compared with patients in the Control Group.

  3. Rate of decline of Lung Function: Patients receiving Early Photopheresis Intervention will have a 50% or greater reduction in the rate of Forced Expiratory Volume [ Time Frame: 12 months following randomization ]
    Forced Expiratory Volume decline as assessed by comparing the average rate of Forced Expiratory Volume decline over the 6 months prior to Treatment against the average rate of Forced Expiratory Volume decline over the 12 months following randomization.


Secondary Outcome Measures :
  1. A) Average rate of Forced Expiratory decline over the 9 months following initiation of Extracorporeal Photopheresis or randomization; [ Time Frame: 9 Months following initiation of ECP (in REFRACTORY BOS or randomization in the RCT ]
    All Patients


Other Outcome Measures:
  1. All-cause mortality annually for five years following either randomization or initiation of treatment in patients with refractory Bronchiolitis Obliterans Syndrome; [ Time Frame: Five years following either randomization or initiation of treatment in patients with refractory bronchiolits obliterans ]
    All Patients

  2. Proportion of patients with treatment-related serious adverse events after randomization or after Extracorporeal Photopheresis initiation . [ Time Frame: 5 years ]
    All Patients

  3. Change in Quality of Life in all patients from Baseline months 3,6,9,12, and annually up to 5 years. [ Time Frame: 5 years ]
    The Quality of Life Questionnaire has combined the Dyspnea 12, the Modified Medical Research Council Dyspnea Scale, The St Georges' Respiratory Questionnaire, and the EQ-5D-5L. The Dyspnea12 questionnaire assesses dyspnea severity and is comprised of 12 items and two domains (Physical: 7 questions, affective: 5 questions). Participants are instructed to indicate how much (None =0, Mild=1, Moderate=2, Severe=3) each item "troubled you". The Modified Medical Research Council Dyspnea Scale comprises 5 statements that describe the range of respiratory disability from none (Grade 0 ) to almost complete incapacity (Grade 5). The St. Georges addresses the frequency of respiratory symptoms and the patient's current state. Each question response has a unique weight. The lowest is 0 and the highest is 100. EQ-5D-5L comprises 5 dimensions: mobility, self-care, usual activities, pain and anxiety/depression.The Scores will be totaled and compared between the two groups.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION Criteria for REFRACTORY BOS

  1. Age (18 years old or older).
  2. Medicare-eligible (i.e., patients with both Part A and Part B) status
  3. Lung transplant recipient (combined organ transplant recipients, e.g. heart-lung or liver-lung recipients, are eligible).
  4. Patients with a diagnosis of BOS using at least two laboratory based FEV1 values obtained at least three weeks apart that are both at least 20% lower than baseline FEV1 using the International Society for Heart and Lung Transplantation (ISHLT) definition (The average of the two highest FEV1 measurements obtained at least 3 weeks apart after transplantation).
  5. Refractory 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.
  6. At minimum five recorded FEV1 measurements obtained at intervals of at least two weeks apart, over the 6 months preceding study enrollment, of which one FEV1 must be within two weeks prior to enrollment.
  7. History of frequent spirometry monitoring defined as having had regular FEV1 measurements during the preceding four months prior to enrollment with no time interval between FEV1 measurements that exceeds 8 weeks.
  8. A documented clinical assessment including a physical assessment and Complete Blood Count (CBC) with White Blood Cell Count (WBC) within two weeks prior to enrollment.

INCLUSION criteria for NEWLY Diagnosed BOS

  1. Age (18 years old or older)
  2. Medicare-eligible status (i.e., patients with both Part A and Part B)
  3. Lung transplant recipient (combined organ transplant recipients, e.g. heart-lung or liver-lung recipients, are eligible).
  4. History of close FEV1 monitoring prior to diagnosis of new BOS defined as having had either of the two monitoring approaches:

    Frequent laboratory based spirometry defined as having had regular FEV1 measurements during the preceding six months prior to diagnosis of new BOS with no time interval between FEV1 measurements that exceeds 8 weeks.

    Frequent Home Spirometry through a Standardized Home Spirometry Method: this Method is currently IRB approved and will be utilized to meet this close monitoring enrollment criteria.

  5. Diagnosis of new BOS (i.e., "new BOS" is defined as within six weeks of enrollment) based on laboratory-based spirometric FEV1 measurements obtained on at least two separate occasions (i.e., at least 3 weeks apart) that have declined by more than 20% from post-transplant baseline values (i.e., using ISHLT definition). Inherent to the diagnosis of new BOS is the exclusion of other potential causes of allograft dysfunction such as acute rejection, respiratory tract infection, and airway anastomotic complications. Thus, sites are encouraged to conduct appropriate evaluation for declining allograft function including bronchoscopy with bronchoalveolar lavage (BAL) and lung biopsies if clinically appropriate to exclude other potential causes of allograft dysfunction.
  6. Achievement of a statistically significant rate of decline in lung function (FEV1) at the diagnosis of new BOS per the criteria in Section 3.6 as assessed by the following criteria:

    For patients who are monitored with laboratory based spirometry, at least five recorded FEV1 measurements obtained at intervals of at least two weeks apart, over the 6 months preceding study enrollment accompanied by a statistically significant (p<0.05) rate of decline of FEV1 that exceeds 30 mL/month; or For patients who are monitored with home Spirometry, the Standardized Home Spirometry Method will define the specific criteria that will be used for these patients.

  7. Documented clinical assessment including a physical assessment and a CBC with WBC within two weeks prior to enrollment.

EXCLUSION Criteria (Subjects meeting any one of these criteria will be excluded)

  1. Current participation in another clinical treatment trial with an investigational agent.
  2. Any condition that may interfere with the subject's ability to perform pulmonary function testing.
  3. Known allergy or hypersensitivity to pharmacologic agents used during ECP
  4. 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 a) patients with a 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, respiratory distress; or b) patients with lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum, albinism, or other dermatologic or ocular condition that contraindicates the use of methoxsalen or markedly enhances photosensitivity in the investigator's judgment.
  5. Aphakia or absence of ocular lenses
  6. Pregnancy (positive pregnancy test - a urine or blood pregnancy test must be obtained within 2 weeks prior to enrollment in women of childbearing potential)
  7. Inability to provide informed consent or to comply with study treatments or assessments (e.g. due to cognitive impairment or geographic distance)
  8. Recent (i.e., within 2 weeks prior to enrollment) leukopenia (white blood cell count < 3,000 K/cumm)
  9. Patients whose decline in lung function (FEV1) is related to either Restrictive Chronic Lung Allograft Dysfunction (CLAD) or other causes that do not represent BOS such as pneumonia, heart failure, etc.

    For patients under review for eligibility for ECP for refractory BOS:

  10. The most recent FEV1 < 900 mL
  11. Rate of FEV1 decline within the last 6 months > 300 mL/month.

    For patients under review for eligibility for RCT:

  12. any patient who at least one year after transplant is treated with either lymphocyte depleting therapy or with an escalated dose of steroids (i.e., prednisone greater than 30 mg/day) for more than one month for an acute decline in lung function that is suspected to be secondary to acute cellular rejection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02181257


Contacts
Layout table for location contacts
Contact: Mary Clare Derfler, RN, MSN 314-747-2372 derflerm@mir.wustl.edu

Locations
Show Show 22 study locations
Sponsors and Collaborators
Washington University School of Medicine
Centers for Medicare and Medicaid Services
Mallinckrodt
Investigators
Layout table for investigator information
Principal Investigator: George J. Despotis, M.D. Washington University St. Louis School of Medicine
Additional Information:

Publications of Results:
Reviewed in: Centers for Medicare and Medicaid Services. Final Decision Memorandum for Extracorporeal Photophresis (CAG-00324R), April 2012

Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02181257    
Other Study ID Numbers: CAG-00324R2-201402035
First Posted: July 3, 2014    Key Record Dates
Last Update Posted: February 21, 2020
Last Verified: February 2020
Keywords provided by Washington University School of Medicine:
Bronchiolitis Obliterans Syndrome
Lung Transplantation
Extracorporeal Photopheresis
Methoxsalen
Additional relevant MeSH terms:
Layout table for MeSH terms
Bronchiolitis
Bronchiolitis Obliterans
Syndrome
Disease
Pathologic Processes
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections