AntiCoagulant Effectiveness in Idiopathic Pulmonary Fibrosis
Condition: Idiopathic Pulmonary Fibrosis
MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis
Intervention: warfarin; placebo
Intervention description: Oral warfarin (1mg or 2.5mg) titrated to an INR of 2-3.; Oral placebo (1mg or 2.5mg)
Intervention MeSH terms: Warfarin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 145.0
Sex: All
Minimum age: 35 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: IPF; Warfarin

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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:

               1. Worsened dyspnea

               2. FVC decreased by >=10% predicted OR

               3. DLCO decreased by >=10% absolute OR

               4. Reduction of oxygenation saturation >= 5% with or without exertion on a constant
                  oxygen (02) administration

               5. Worsened radiographic findings (chest x-ray or high-resolution computed
                  tomography)

        Exclusion Criteria:

          -  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:

               1. 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.

               2. Subject has a transplanted organ requiring immunosuppression

               3. 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).

               4. 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.

          -  Anticoagulation-related exclusions include:

               1. Current anticoagulation therapy with warfarin

               2. Increased risk of bleeding (e.g. uncorrectable inherited or acquired bleeding
                  disorder)

               3. Platelet count < 100,000 or hematocrit < 30% or > 55%

               4. History of severe gastrointestinal bleeding within 6 months of screening

               5. History of cerebral vascular accident (CVA) within 6 months of screening

               6. High risks of falls as judged by the PI

               7. Surgery or major trauma within the past 30 days

               8. Pregnancy, or lack of use of birth control method in women of childbearing age

               9. Any condition that, in the determination of the PI, is likely to require
                  anticoagulation therapy during the study.

              10. Clopidogrel and aspirin combination therapy for > 30 days duration is
                  exclusionary.

                  (Aspirin monotherapy [81-325 mg daily] or clopidogrel monotherapy are acceptable.
                  Combination clopidogrel and aspirin <=81mg/day for ≤30 days is also acceptable.
                  NSAIDS are discouraged; acetaminophen may be substituted.)

              11. Patients on prasugrel are excluded. Prasugrel must be stopped for one week prior
                  to starting study drug.