AntiCoagulant Effectiveness in Idiopathic Pulmonary Fibrosis

NCT00957242 | Terminated Phase 3 Results DMC

• 3 other identifiers: Pro000171565U10HL080413-05671
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 22

Brief Summary

This study will test the effectiveness of warfarin in patients with IPF. Approximately 256 patients will be randomized 1:1 to either warfarin or placebo. Patients will return at week 1 for a safety review and every 16 weeks for 48 weeks. The primary endpoint in the study is the time to either death, non-bleeding/non-elective hospitalization, or a drop of greater than 10% in forced vital capacity (FVC) from baseline.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

IPF; Warfarin

Outcome Measures

Primary Outcomes (1)

• Death, Non-bleeding/Non-elective Hospitalization, or >10% Drop in Forced Vital Capacity

  Death, non-bleeding/non-elective hospitalization, or \>10% drop in forced vital capacity.

  Events up to 48 weeks

Secondary Outcomes (11)

• All Cause Mortality

  maximum of 48 weeks

• Change in Forced Vital Capacity (FVC) From Baseline to 16 Weeks

  16 weeks

• All-cause Hospitalizations

  maximum 48 weeks

• Bleeding Events

  maximum of 48 weeks

• Acute Exacerbations of Idiopathic Pulmonary Fibrosis (IPF)

  maximum of 48 weeks

Study Arms (2)

warfarin

ACTIVE COMPARATOR

Oral warfarin titrated to an international normalization ratio (INR) of 2-3

Drug: warfarin

placebo

PLACEBO COMPARATOR

Oral placebo (1mg or 2.5mg)

Drug: placebo

Interventions

warfarin DRUG

Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.

Also known as: warfarin sodium

warfarin

placebo DRUG

Oral placebo (1mg or 2.5mg)

placebo

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of IPF
• Age between 35 and 80, inclusive
• Capable of understanding and signing consent
• Progression despite conventional therapy (standard of care). Progression defined as:
• Worsened dyspnea
• FVC decreased by \>=10% predicted OR
• DLCO decreased by \>=10% absolute OR
• Reduction of oxygenation saturation \>= 5% with or without exertion on a constant oxygen (02) administration
• Worsened radiographic findings (chest x-ray or high-resolution computed tomography)

You may not qualify if:

• Current enrollment in another investigational protocol
• Current treatment with an investigational drug (i.e., participating in an active investigational drug protocol) within the previous 4 weeks or 5 times the half-life of the investigational agent, whichever is longer, prior to screening
• Subject is actively listed for lung transplantation at the time of enrollment
• Subjects who will not be able to perform/complete the study, in the judgment of the physician investigator or coordinator, for at least 3 months. For example:
• Subject has current signs or symptoms of severe, progressive or uncontrolled comorbid illnesses such as: renal, hepatic, hematologic, gastrointestinal, endocrine, cardiac, neurologic, or cerebral disease, or any laboratory abnormality which would pose/suggest a risk to the subject during participation in the study.
• Subject has a transplanted organ requiring immunosuppression
• History of substance abuse (drugs or alcohol) within the 2 years prior to screening, history of noncompliance to medical regimens, inability or unwillingness to perform INR monitoring, or other condition/circumstance that could interfere with the subject's adherence to protocol requirements (e.g. psychiatric disease, lack of motivation, travel, etc).
• Have any known active malignancy or have a history of malignancy within the previous 2 years (an example of an exception is a non-melanoma skin cancer that has been treated with no evidence of recurrence for at least 3 months) that might increase the risk of bleeding.
• Estimated life expectancy \< 12 months due to a non-pulmonary cause.
• Subject has another respiratory disease that is predominant (as judged by the PI) in addition to IPF.
• Current anticoagulation therapy with warfarin
• Increased risk of bleeding (e.g. uncorrectable inherited or acquired bleeding disorder)
• Platelet count \< 100,000 or hematocrit \< 30% or \> 55%
• History of severe gastrointestinal bleeding within 6 months of screening
• History of cerebral vascular accident (CVA) within 6 months of screening

Sponsors & Collaborators

• Duke University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Duke Clinical Research Institute: collaborator

Study Sites (22)

University of Alabama - Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California - Los Angeles

Los Angeles, California, 90095, United States

Location

University of California - San Francisco

San Francisco, California, 94110, United States

Location

National Jewish Medical and Research Center

Denver, Colorado, 80206, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520-8057, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Louisville

Louisville, Kentucky, 40425, United States

Location

Tulane University

New Orleans, Louisiana, 70118, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

St. Luke's Hospital

Chesterfield, Missouri, 63017, United States

Location

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

Highland Hospital - University of Rochester Medical Center

Rochester, New York, 14620, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Utah Health Research Center

Salt Lake City, Utah, 84108, United States

Location

University of Washington

Seattle, Washington, 98165, United States

Location

Related Publications (4)

• Allen RJ, Stockwell A, Oldham JM, Guillen-Guio B, Schwartz DA, Maher TM, Flores C, Noth I, Yaspan BL, Jenkins RG, Wain LV; International IPF Genetics Consortium. Genome-wide association study across five cohorts identifies five novel loci associated with idiopathic pulmonary fibrosis. Thorax. 2022 Aug;77(8):829-833. doi: 10.1136/thoraxjnl-2021-218577. Epub 2022 Jun 10.

  PMID: 35688625 DERIVED

• Andrade J, Schwarz M, Collard HR, Gentry-Bumpass T, Colby T, Lynch D, Kaner RJ; IPFnet Investigators. The Idiopathic Pulmonary Fibrosis Clinical Research Network (IPFnet): diagnostic and adjudication processes. Chest. 2015 Oct;148(4):1034-1042. doi: 10.1378/chest.14-2889.

  PMID: 26111071 DERIVED

• Durheim MT, Collard HR, Roberts RS, Brown KK, Flaherty KR, King TE Jr, Palmer SM, Raghu G, Snyder LD, Anstrom KJ, Martinez FJ; IPFnet investigators. Association of hospital admission and forced vital capacity endpoints with survival in patients with idiopathic pulmonary fibrosis: analysis of a pooled cohort from three clinical trials. Lancet Respir Med. 2015 May;3(5):388-96. doi: 10.1016/S2213-2600(15)00093-4. Epub 2015 Apr 15.

  PMID: 25890798 DERIVED

• Noth I, Anstrom KJ, Calvert SB, de Andrade J, Flaherty KR, Glazer C, Kaner RJ, Olman MA; Idiopathic Pulmonary Fibrosis Clinical Research Network (IPFnet). A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2012 Jul 1;186(1):88-95. doi: 10.1164/rccm.201202-0314OC. Epub 2012 May 3.

  PMID: 22561965 DERIVED

Related Links

• IPFnet Web Site

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

Warfarin

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Imre Noth, MD, Associate Professor of Medicine
• Organization: University of Chicago Hospital

inoth@medicine.bsd.uchicago.edu

773-834-1832

Study Officials

• Galen Toews, MD

  University of Michigan

  STUDY CHAIR

• Gail Weinmann, MD

  National Heart, Lung, and Blood Institute (NHLBI)

  STUDY DIRECTOR

• Kevin Brown, MD

  National Jewish Health

  PRINCIPAL INVESTIGATOR

• Rob Kaner, MD

  Weill Medical College at Cornell University

  PRINCIPAL INVESTIGATOR

• Talmadge King, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Joe Lasky, MD

  Tulane University School of Medicine

  PRINCIPAL INVESTIGATOR

• James Loyd, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

• Fernando Martinez, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Imre Noth, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

• Ganesh Raghu, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

• Jesse Roman, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Jay Ryu, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Joseph Lynch, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Kevin Anstrom, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

• Joao deAndrade, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Jeffrey Chapman, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

• Lake Morrison, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Michael Kallay, MD

  Highland Hospital

  PRINCIPAL INVESTIGATOR

• Steven Sahn, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

• Marilyn Glassberg, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

• Milton Rossman, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• John Fitzgerald, MD

  University of Texas

  PRINCIPAL INVESTIGATOR

• Mary Beth Scholand, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

• Neil Ettinger, MD

  St. Luke's Hospital

  PRINCIPAL INVESTIGATOR

• Danielle Antin-Ozerkis, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2009
• First Posted: August 12, 2009
• Study Start: October 1, 2009
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: July 23, 2014
• Results First Posted: October 21, 2013

Record last verified: 2013-04

Locations

US (22)