Osteoarthritis of the Knee, Coagulopathy
Conditions
Keywords
Knee pain, Anticoagulant, Warfarin, Dabigatran, Clopidogrel, Aspirin, Topical NSAID, Osteoarthritis
Brief summary
The purpose of this study is to see if using a topical nonsteroidal antiinflammatory drug (Pennsaid) to treat osteoarthritis knee pain will affect coagulation values in patients who are also taking anticoagulant or antithrombotic medications.
Detailed description
Open-label active treatment Phase III study of Pennsaid (diclofenac sodium 1.5% topical solution) to determine the effects on coagulation parameters in patients who are equal to or greater than 55 years of age with moderate to severe osteoarthritis knee pain and who are also taking warfarin, dabigatran, or aspirin and/or clopidogrel.
Interventions
DRUGPennsaid
Administered 10 drops x 4 until 40 drops applied topically to index knee (and also non-index knee if osteoarthritis pain is present bilaterally) 4 times a day for a 4 week active treatment period.
Sponsors
Medtronic - MITG
Arthritis Treatment Center, Maryland
Nathan Wei, MD, FACP, FACR:
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female adults \> than or equal to 55 * Ambulatory subjects with moderate to severe osteoarthritis (OA) of the knee with symptoms and knee pain for at least 3 months and pain on the majority of days in the last 30 days. * Subjects with bilateral knee OA, the more symptomatic knee is the index knee and PENNSAID can be applied on both knees if both are affected. * Radiographic evidence of Kellgren-Lawrence Grade 2-4 within the past 2 years. * Currently on a stable dose of anticoagulant therapy (warfarin, dabigatran, aspirin or clopidogrel) for the past 2 months and expected to remain on current dose for the six week duration of the study. * If currently taking oral nonsteroidal antiinflammatory drug (NSAID) and/or acetaminophen for OA knee pain, must be taking it for at least an average of 25 days per month. * Those currently taking oral NSAID must be willing to perform a 7 day washout to be eligible to be enrolled into the study. * A pain score of \> than 40mm on the Patient Pain Visual Analog Scale (VAS) (100 mm scale) at screening and baseline visit. * Able to comply with the study and give informed consent prior to performance of any study procedures. * Able to read, write and understand English.
Exclusion criteria
* Unwilling to abstain from oral NSAIDs and/or other analgesic medication except for acetaminophen as rescue medication. Subjects taking low dose aspirin for cardiovascular health may remain on their stable dose throughout the study. * Unwilling to abstain from taking \< than or equal to 1500mg of acetaminophen a day for rescue medication purposes during the 6 week course of the trial. * Using a handicap assistance device i.e. cane, walker \> than or equal to 50% of the time. * Undergoing new physical therapy or participating in a weight loss or exercise program that has not been stable for at least 3 months prior to screening and won't remain stable during participation in study. * History or diagnosis of an inflammatory arthritis i.e. rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis, or amyloidosis. * Known or clinically suspected infection and human immunodeficiency virus (HIV), or hepatitis C or B viruses. * History of abnormal laboratory results \> that or equal to 2.5 x upper limit of normal (ULN) indicative of any significant medical disease which in the opinion of the investigator, would preclude the subjects participation in the study. * Any of the following abnormal laboratory results during screening: * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> than or equal to 2.5 x ULN * Hemoglobin \< than 11.5 g/dL (female) or \< 13.2 g/dL (male) * White blood cell count (WBC) \< than 3500 cells/mm3 * Lymphocyte count \< than or equal to 1000 cels/mm3 * Serum creatinine \> than or equal 1.5 x ULN * Platelet count below the central laboratory lower limit of normal (LLN) * Coagulation tests (Prothrombin Time (PT), Partial Thromboplastin Time (PTT), International Normalized Ratio (INR), Platelet Aggregation) requiring an alteration in anticoagulant dosage. * Skin breakdown or rash at knee where topical PENNSAID is to be applied. * Other serious uncontrolled non-malignant, significant, acute or chronic medical or psychiatric illness that, in judgment of investigator, could compromise subject safety, limit subject's ability to complete study and/or compromise the objectives of study. * History of malignancy in the past 5 years with exception of resected basal cell carcinoma, squamous cell carcinoma of the skin, or resected cervical atypia or carcinoma in situ. * History of drug or alcohol dependence or abuse in the past 3 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 4 in Laboratory Results of Prothrombin Time (PT) | Baseline to week 4 | PT will be evaluated to determine if there is any significant effect of Pennsaid on coagulation parameters. |
| Change From Baseline to Week 4 in Laboratory Results of International Normalized Ratio (INR) | Baseline to Week 4 | INR will be evaluated to determine if there is any significant effect of Pennsaid on coagulation parameters. |
| Change From Baseline to Week 4 in Laboratory Results of Partial Thromboplastin Time (PTT) | Baseline to Week 4 | PTT will be evaluated to determine if there is any significant effect of Pennsaid on coagulation parameters. |
| Change From Baseline to Week 4 in Laboratory Results of Platelet Aggregation | Baseline to Week 4 | Platelet Aggregation will be evaluated to determine if there is any significant effect of Pennsaid on coagulation parameters. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pennsaid, Warfarin Pennsaid 1.5%, 10 drops x 4 until 40 drops applied topically to index knee (and also non-index knee if OA pain is present bilaterally) 4 times a day for a 4 week active treatment period in a subject who has been taking a stable dose of warfarin for at least 2 months
Pennsaid: Administered 10 drops x 4 until 40 drops applied topically to index knee (and also non-index knee if OA pain is present bilaterally) 4 times a day for a 4 week active treatment period. | 9 |
| Pennsaid, Dabigatran Pennsaid 1.5%, 10 drops x 4 until 40 drops applied topically to index knee (and also non-index knee if OA pain is present bilaterally) 4 times a day for a 4 week active treatment period in a subject who has been taking a stable dose of dabigatran for at least 2 months
Pennsaid: Administered 10 drops x 4 until 40 drops applied topically to index knee (and also non-index knee if OA pain is present bilaterally) 4 times a day for a 4 week active treatment period. | 5 |
| Pennsaid, Aspirin and/or Clopidogrel Pennsaid 1.5%, 10 drops x 4 until 40 drops applied topically to index knee (and also non-index knee if OA pain is present bilaterally) 4 times a day for a 4 week active treatment period in a subject who has been taking a stable dose of aspirin and/or clopidogrel for at least 2 months
Pennsaid: Administered 10 drops x 4 until 40 drops applied topically to index knee (and also non-index knee if OA pain is present bilaterally) 4 times a day for a 4 week active treatment period. | 8 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Pennsaid, Warfarin | Pennsaid, Dabigatran | Pennsaid, Aspirin and/or Clopidogrel | Total |
|---|---|---|---|---|
| Age, Customized > / = 55 years | 9 participants | 5 participants | 8 participants | 22 participants |
| Region of Enrollment United States | 9 participants | 5 participants | 8 participants | 22 participants |
| Sex: Female, Male Female | 8 Participants | 2 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 9 | 0 / 5 | 4 / 10 |
| serious Total, serious adverse events | 1 / 9 | 0 / 5 | 0 / 10 |
Outcome results
Primary
Change From Baseline to Week 4 in Laboratory Results of International Normalized Ratio (INR)
INR will be evaluated to determine if there is any significant effect of Pennsaid on coagulation parameters.
Time frame: Baseline to Week 4
Population: Two subjects who completed the study were taking both an anticoagulant medication and aspirin. For this analysis, the subject who was taking warfarin and aspirin was included only in the Pennsaid, warfarin group, and the subject who was taking dabigatran and aspirin was included only in the Pennsaid, dabigatran group.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pennsaid, Warfarin | Change From Baseline to Week 4 in Laboratory Results of International Normalized Ratio (INR) | 0.63 ratio |
| Pennsaid, Dabigatran | Change From Baseline to Week 4 in Laboratory Results of International Normalized Ratio (INR) | 0.09 ratio |
| Pennsaid, Aspirin and/or Clopidogrel | Change From Baseline to Week 4 in Laboratory Results of International Normalized Ratio (INR) | 0.00 ratio |
Primary
Change From Baseline to Week 4 in Laboratory Results of Partial Thromboplastin Time (PTT)
PTT will be evaluated to determine if there is any significant effect of Pennsaid on coagulation parameters.
Time frame: Baseline to Week 4
Population: Two subjects who completed the study were taking both an anticoagulant medication and aspirin. For this analysis, the subject who was taking warfarin and aspirin was included only in the Pennsaid, warfarin group, and the subject who was taking dabigatran and aspirin was included only in the Pennsaid, dabigatran group.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pennsaid, Warfarin | Change From Baseline to Week 4 in Laboratory Results of Partial Thromboplastin Time (PTT) | 2.68 Seconds |
| Pennsaid, Dabigatran | Change From Baseline to Week 4 in Laboratory Results of Partial Thromboplastin Time (PTT) | 1.50 Seconds |
| Pennsaid, Aspirin and/or Clopidogrel | Change From Baseline to Week 4 in Laboratory Results of Partial Thromboplastin Time (PTT) | -0.29 Seconds |
Primary
Change From Baseline to Week 4 in Laboratory Results of Platelet Aggregation
Platelet Aggregation will be evaluated to determine if there is any significant effect of Pennsaid on coagulation parameters.
Time frame: Baseline to Week 4
Population: For this analysis, the subject who was taking warfarin and aspirin was included in both the Pennsaid, warfarin group and the Pennsaid, aspirin and/or clopidogrel group, and the subject who was taking dabigatran and aspirin was included in both the Pennsaid, dabigatran group and the Pennsaid, aspirin and/or clopidogrel group.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pennsaid, Warfarin | Change From Baseline to Week 4 in Laboratory Results of Platelet Aggregation | 8.14 Seconds |
| Pennsaid, Dabigatran | Change From Baseline to Week 4 in Laboratory Results of Platelet Aggregation | -39.25 Seconds |
| Pennsaid, Aspirin and/or Clopidogrel | Change From Baseline to Week 4 in Laboratory Results of Platelet Aggregation | -13.30 Seconds |
Primary
Change From Baseline to Week 4 in Laboratory Results of Prothrombin Time (PT)
PT will be evaluated to determine if there is any significant effect of Pennsaid on coagulation parameters.
Time frame: Baseline to week 4
Population: Two subjects who completed the study were taking both an anticoagulant medication and aspirin. For this analysis, the subject who was taking warfarin and aspirin was included only in the Pennsaid, warfarin group, and the subject who was taking dabigatran and aspirin was included only in the Pennsaid, dabigatran group.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pennsaid, Warfarin | Change From Baseline to Week 4 in Laboratory Results of Prothrombin Time (PT) | 6.97 seconds |
| Pennsaid, Dabigatran | Change From Baseline to Week 4 in Laboratory Results of Prothrombin Time (PT) | 0.96 seconds |
| Pennsaid, Aspirin and/or Clopidogrel | Change From Baseline to Week 4 in Laboratory Results of Prothrombin Time (PT) | -0.04 seconds |