Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 11 of 104 for:    Recruiting, Not yet recruiting, Available Studies | (idiopathic pulmonary fibrosis)

Autoantibody Reduction for Acute Exacerbations of Idiopathic Pulmonary Fibrosis (STRIVE-IPF)

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: NCT03286556
Recruitment Status : Recruiting
First Posted : September 18, 2017
Last Update Posted : September 13, 2019
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Brigham and Women's Hospital
Temple University
University of Pittsburgh
Information provided by (Responsible Party):
Steven R. Duncan, MD, University of Alabama at Birmingham

Tracking Information
First Submitted Date  ICMJE September 12, 2017
First Posted Date  ICMJE September 18, 2017
Last Update Posted Date September 13, 2019
Actual Study Start Date  ICMJE September 4, 2018
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2017)
Survival [ Time Frame: 6 months ]
Actuarial survival
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03286556 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2017)
  • Oxygen requirements [ Time Frame: 6 months ]
    Measures of oxygen required to maintain arterial oxygen concentration (SaO2) >/=93%
  • Walk distance [ Time Frame: 6 months ]
    6 minute walk distance using standardized American Thoracic Society/European Respiratory Society (ATS/ERS) protocols.
  • Adverse Events [ Time Frame: Through study completion, an average of 1 year ]
    The presence of adverse events attributable to the trial intervention
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autoantibody Reduction for Acute Exacerbations of Idiopathic Pulmonary Fibrosis
Official Title  ICMJE Study of Therapeutic Plasma Exchange, Rituximab and Intravenous Immunoglobulin for Acute Exacerbations of Idiopathic Pulmonary Fibrosis (STRIVE-IPF)
Brief Summary

Acute exacerbations (AE) are a dreaded manifestation of idiopathic pulmonary fibrosis (IPF) that presents with rapidly worsening respiratory function over days to weeks. AE account for about 1/2 the deaths in IPF patients, and are refractory to all medical therapies attempted to date.

Considerable preliminary data shows pathological B-cell abnormalities and autoantibodies are present in AE-IPF and associated with disease severity.

The experimental therapy here (therapeutic plasma exchange plus rituximab plus intravenous immunoglobulin) is mechanistically targeted to ameliorate autoantibody-mediated pulmonary injury. Anecdotal pilot studies indicate these treatments have significant benefit for a disease syndrome that has, until now, been almost invariably inexorable. This clinical trial has the potential to profoundly affect current paradigms and treatment approaches to patients with AE-IPF.

Detailed Description

The primary goal of clinical trial is to determine effects of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG) in comparison to effects of treatment as usual (TAU), among AE-IPF patients.

Our central hypothesis is "AUTOANTIBODY REDUCTION IS BENEFICIAL FOR AE-IPF PATIENTS." A corollary of this hypothesis is that antibody-mediated autoimmunity can play an important role in IPF exacerbations.

Following baseline screening assessments, hospitalized AE-IPF patients at the collaborating sites that meet all inclusion/exclusion criteria will be randomly assigned to receive one of the following treatments in a ratio of 2:1:

• Arm A (n=34) - Experimental Treatment:

Steroids: Prednisone 60 mg (p.o.) on day 1, followed by 20 mg/day on days 2-5, 7-14, and 16-19 (or the i.v. methylprednisolone equivalent). Methyl-prednisolone 100 mg i.v. will be administered on days 6 and 15, as a premedication prior to the rituximab.

Insertion of a dialysis/apheresis catheter into a central vein, and initiation of therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG) regimens:

Therapeutic Plasma Exchange (TPE) will consist of 1x estimated plasma volume exchanges for 3 successive days (1-3) and then, after a one day interval to enable equilibration of autoantibodies between intra- and extra-vascular spaces, again on days 5, 6, 9, 11, 13, and 15.

Rituximab: One gm i.v. will be administered on day 6 and day 15 after completion of the TPE on those days.

Intravenous immunoglobulin (IVIG): 0.5 gm/kg/day i.v. on days 16-19

• Arm B (n=17) - Treatment as Usual (TAU):

The same steroid regimen as described for Arm A, i.e., prednisone 60 mg (p.o.) on day 1, followed by 20 mg/day on days 2-5, 7-14, and 16-19 (or the i.v. methylprednisolone equivalent), and methylprednisolone 100 mg i.v. administered on days 6 and 15.

All patients enrolled in both cohorts at all sites will also receive empiric broad-spectrum antibiotics for 8 days. The empiric antibiotic regimen will be reassessed and tailored based on any subsequent cultures and sensitivity results.

Patients will be monitored carefully for occurrences of adverse events, laboratory test abnormalities, and changes in vital signs.

The respective treatment courses can be finished on an outpatient basis among enrolled patients who are able to be discharged from the hospital, if medically indicated, and if those treatment compliance can be assured.

Patients will be followed for the duration of their hospital admission after enrollment, and then observed as either inpatients or outpatients on days 19, 60, 90, 180, 270, and 365. A telephone contact will occur at monthly intervals, aside from those visits above. The total observation/subject is 365 days.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Open label randomized controlled trial.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Idiopathic Pulmonary Fibrosis, Acute Fatal Form
Intervention  ICMJE
  • Drug: Autoantibody Reductive Therapy
    TPE x 9, rituximab x 2, IVIG x 4. See arm/group descriptions for additional details.
  • Drug: Treatment as Usual (TAU)
    Antibiotics and steroids
    Other Name: Antibiotics and steroids
Study Arms  ICMJE
  • Experimental: Autoantibody Reductive Therapy

    Therapeutic Plasma Exchange (TPE) consisting of 1x estimated plasma volume exchanges for 3 successive days (1-3) and then, after a one day interval to enable equilibration of autoantibodies between intra- and extra-vascular spaces, again on days 5, 6, 9, 11, 13, and 15.

    Rituximab: One gm i.v. will be administered on day 6 and day 15 after completion of the TPE on those days.

    Intravenous immunoglobulin (IVIG): 0.5 gm/kg/day i.v. on days 16-19

    All subjects in this trial, including patients in this arm, will receive identical empiric antibiotics and steroids. The steroid dose is: Prednisone 60 mg (p.o.) on day 1, followed by 20 mg/day on days 2-5, 7-14, and 16-19 (or the i.v. methylprednisolone equivalent). Methylprednisolone 100 mg i.v. will be administered on days 6 and 15, as a premedication prior to the rituximab.

    Intervention: Drug: Autoantibody Reductive Therapy
  • Active Comparator: Treatment as Usual (TAU)
    The same steroid regimen as described for the experimental arm, i.e., prednisone 60 mg (p.o.) on day 1, followed by 20 mg/day on days 2-5, 7-14, and 16-19 (or the i.v. methylprednisolone equivalent), and methylprednisolone 100 mg i.v. administered on days 6 and 15, as well as empiric antibiotics.
    Intervention: Drug: Treatment as Usual (TAU)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 13, 2017)
51
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 30, 2022
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age between 40-85 years old.
  2. A diagnosis of IPF that fulfills ATS/ERS Consensus Criteria.1
  3. Worsening or new development of dyspnea or hypoxemia within the last 30 days.
  4. Ground-glass abnormality and/or consolidation superimposed on a reticular or honeycomb usual interstitial pneumonitis (UIP) pattern on locally read chest CT scan.
  5. Ability and willingness to give informed consent (no surrogates) and adhere to study requirements.

Exclusion Criteria:

  1. Diagnoses of current infection per clinical or microbial assessments.
  2. Diagnoses of an additional or alternative etiology for respiratory dysfunction based upon clinical assessment, including congestive heart failure, sepsis, thromboembolism, etc.
  3. History or serologic evidence of hepatitis B or C infection.
  4. Coagulopathy, defined as a International Normalized Ratio (INR) >1.6, partial thromboplastin time (PTT) > 2x control, fibrinogen <100 mg/dL, or platelet count <50 thousand (K) unless these abnormalities can be reversed safely.
  5. Hyperosmolar state or diabetic ketoacidosis to suggest uncontrolled diabetes, or uncontrolled hypertension (systolic BP >160 mm Hg and diastolic BP >100 mm Hg) that would contraindicate use of corticosteroids.
  6. Hemodynamic instability, defined as an inotrope or vasopressor requirement.
  7. History of reaction to blood products or murine-derived products or prior rituximab use.
  8. History of malignancy, excluding basal or squamous cell skin cancer and low-risk prostate cancer, the latter defined as stage T1 or T2a, with prostate specific antigen (PSA) less than 10 ng/dl. The experimental treatments are not known to promote cancer progression, and these criteria are within current guidelines.
  9. Unwillingness to accept blood product transfusion.
  10. Diagnosis of major comorbidities expected to interfere with study participation.
  11. Treatment for >14 days within the preceding month with >20 mg. prednisone (or equivalent) or any treatment during the last month with a cellular immuno-suppressant (e.g., cyclophosphamide, methotrexate, calcineurin inhibitors, mycophenolate, azathioprine, etc.). An exception will be made if the patient has a bronchoalveolar lavage (BAL) negative for pathogens.
  12. Current treatment with an angiotensin converting enzyme inhibitor that cannot be discontinued and/or substituted (to obviate hemodynamic complications during TPE).
  13. Concurrent participation in other experimental trials.
  14. Fertile females who do not agree to contraception or abstinence, or have a positive pregnancy test (urine or blood). IPF is a disease of older adults, and male predominant, so this will not be a frequent consideration.
  15. Presence of positive (abnormal) classical autoimmune tests: anti-nuclear antibody (ANA), rheumatoid factor (RF), Anti- Sjögren's-syndrome-related antigen (SSA) , and Anti-Cyclic Citrullinated Peptide (CCP). This criterion will eliminate patients with confounding classical autoimmune syndromes. Many IPF patients will have already had these tests, which are standard of practice (SOP) at many IPF centers, and these prior results will suffice if the tests were performed within the last year. Otherwise, these tests need to be performed prior to enrollment and they can usually be procured in 1-2 days. Based on experience, we anticipate ~10% of patients who fulfill all other IPF criteria will nonetheless be positive for one of these classical autoantibody tests.
  16. IgA deficiency (IgA level <7 mg/dL)- to preclude IVIG reactions.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Steven R Duncan, MD 205-934-5018 srduncan@uabmc.edu
Contact: Melissa D Garner, RN 205-934-6229 mdgarnder@uabmc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03286556
Other Study ID Numbers  ICMJE F170530011
1U01HL133232-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Steven R. Duncan, MD, University of Alabama at Birmingham
Study Sponsor  ICMJE University of Alabama at Birmingham
Collaborators  ICMJE
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Brigham and Women's Hospital
  • Temple University
  • University of Pittsburgh
Investigators  ICMJE Not Provided
PRS Account University of Alabama at Birmingham
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP