Rheumatoid Arthritis
Conditions
Brief summary
The study will compare the effects of prednisone vs placebo on synovial blood flow and overall DAS (disease activity score) in patients with rheumatoid arthritis.
Interventions
DRUGPrednisone 15 mg
Prednisone 15 mg tablets once daily for 15 days.
DRUGPlacebo Tablets
Prednisone placebo tablets once daily for 15 days.
DRUGPrednisone 7.5 mg
Prednisone 7.5 mg over-encapsulated tablets once daily for 15 days
DRUGPlacebo Over-Encapsulated Tablets
Prednisone 7.5 mg placebo over-encapsulated tablets once daily for 15 days
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient is willing to limit alcohol intake to 3 or less beverages per day * Patient agrees to use only acetaminophen/paracetamol for breakthrough pain
Exclusion criteria
* Patient has other inflammatory arthritis (e.g. lupus). Patient has had major surgery or donated or lost 1 unit of blood in the last 4 weeks * Patient has a history of drug or alcohol abuse in the last 2 years * Patient has had a vaccine (with a live or attenuated virus) in the last two weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Synovial Blood Flow | Baseline and Day 14 | Synovial Blood Flow was measured as the 2-dimensional quantitative Transverse Power Doppler Area summed over each of the 10 metacarpophalangeal joints (10MCP 2D Trans PDA). The PDA is a count of the number of pixels with power Doppler signal, uncorrected by pixel intensity, within an expert drawn region of interest encompassing the synovium and excluding digital vessels in a standardized 2D transverse image of the joint. A higher pixel count relates to greater synovial blood flow. A decrease in pixel count relates to a reduction in synovial blood flow. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP]) | Baseline and Day 14 | The DAS28(CRP) is a measure of disease activity with components which include the tender joint count (TJC) & swollen joint count (SJC) (each out of 28 joints counted), a Global Health (GH) index (100 mm visual analog scale \[VAS\]), and the CRP (in mg/L measured from lab test). The scoring formula was: DAS28(CRP) = 0.56\*SQR(TJC28) + 0.28\*SQR(SJC28) + 0.36\*ln(CRP+1) + 0.014\*GH(VAS) + 0.96. Where SQR is square root and ln is natural log. The formula produces a score from 0 to 10: \>5.1 means high disease activity; \<3.2 means low disease activity, \<2.6 is generally considered remission. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prednisone 15 mg Prednisone 15 mg tablets once daily for 15 days | 8 |
| Placebo 15 mg Prednisone 15 mg placebo tablets once daily for 15 days | 10 |
| Prednisone 7.5 mg Prednisone 7.5 mg over-encapsulated tablets once daily for 15 days
As per adaptive dose-ranging design, this arm was added to the study because a difference between prednisone 15 mg and placebo was demonstrated during interim analysis. | 18 |
| Placebo 7.5 mg Prednisone 7.5 mg placebo over-encapsulated tablets once daily for 15 days
As per adaptive dose-ranging design, this arm was added to the study because a difference between prednisone 15 mg and placebo was demonstrated during interim analysis. | 9 |
| Total | 45 |
Baseline characteristics
| Characteristic | Prednisone 15 mg | Placebo 15 mg | Prednisone 7.5 mg | Placebo 7.5 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 61.6 years | 58.4 years | 57.9 years | 55.1 years | 58.1 years |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 12 Participants | 6 Participants | 29 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 6 Participants | 3 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 8 | 4 / 10 | 6 / 18 | 2 / 9 |
| serious Total, serious adverse events | 0 / 8 | 0 / 10 | 0 / 18 | 1 / 9 |
Outcome results
Primary
Synovial Blood Flow
Synovial Blood Flow was measured as the 2-dimensional quantitative Transverse Power Doppler Area summed over each of the 10 metacarpophalangeal joints (10MCP 2D Trans PDA). The PDA is a count of the number of pixels with power Doppler signal, uncorrected by pixel intensity, within an expert drawn region of interest encompassing the synovium and excluding digital vessels in a standardized 2D transverse image of the joint. A higher pixel count relates to greater synovial blood flow. A decrease in pixel count relates to a reduction in synovial blood flow.
Time frame: Baseline and Day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone 15 mg | Synovial Blood Flow | Baseline | 9.48 pixel count | Standard Deviation 6.44 |
| Prednisone 15 mg | Synovial Blood Flow | Day 14 | 6.52 pixel count | Standard Deviation 6.4 |
| Prednisone 15 mg | Synovial Blood Flow | Change from Baseline at Day 14 | -2.96 pixel count | Standard Deviation 5.07 |
| Placebo 15 mg | Synovial Blood Flow | Day 14 | 13.37 pixel count | Standard Deviation 11.05 |
| Placebo 15 mg | Synovial Blood Flow | Change from Baseline at Day 14 | 2.82 pixel count | Standard Deviation 4.62 |
| Placebo 15 mg | Synovial Blood Flow | Baseline | 10.55 pixel count | Standard Deviation 9.54 |
| Prednisone 7.5 mg | Synovial Blood Flow | Baseline | 8.31 pixel count | Standard Deviation 8.66 |
| Prednisone 7.5 mg | Synovial Blood Flow | Change from Baseline at Day 14 | -3.88 pixel count | Standard Deviation 5.71 |
| Prednisone 7.5 mg | Synovial Blood Flow | Day 14 | 4.44 pixel count | Standard Deviation 4.94 |
| Placebo 7.5 mg | Synovial Blood Flow | Day 14 | 9.15 pixel count | Standard Deviation 11.65 |
| Placebo 7.5 mg | Synovial Blood Flow | Baseline | 9.78 pixel count | Standard Deviation 7.28 |
| Placebo 7.5 mg | Synovial Blood Flow | Change from Baseline at Day 14 | -0.64 pixel count | Standard Deviation 9.41 |
Secondary
Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP])
The DAS28(CRP) is a measure of disease activity with components which include the tender joint count (TJC) & swollen joint count (SJC) (each out of 28 joints counted), a Global Health (GH) index (100 mm visual analog scale \[VAS\]), and the CRP (in mg/L measured from lab test). The scoring formula was: DAS28(CRP) = 0.56\*SQR(TJC28) + 0.28\*SQR(SJC28) + 0.36\*ln(CRP+1) + 0.014\*GH(VAS) + 0.96. Where SQR is square root and ln is natural log. The formula produces a score from 0 to 10: \>5.1 means high disease activity; \<3.2 means low disease activity, \<2.6 is generally considered remission.
Time frame: Baseline and Day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone 15 mg | Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP]) | Baseline | 5.17 score on scale | Standard Deviation 1.3 |
| Prednisone 15 mg | Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP]) | Change from Baseline at Day 14 | -1.61 score on scale | Standard Deviation 1.69 |
| Prednisone 15 mg | Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP]) | Day 14 | 3.57 score on scale | Standard Deviation 1.5 |
| Placebo 15 mg | Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP]) | Baseline | 5.45 score on scale | Standard Deviation 1.65 |
| Placebo 15 mg | Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP]) | Change from Baseline at Day 14 | -0.41 score on scale | Standard Deviation 0.72 |
| Placebo 15 mg | Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP]) | Day 14 | 5.04 score on scale | Standard Deviation 2.09 |
| Prednisone 7.5 mg | Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP]) | Day 14 | 4.57 score on scale | Standard Deviation 1.12 |
| Prednisone 7.5 mg | Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP]) | Baseline | 5.31 score on scale | Standard Deviation 1.18 |
| Prednisone 7.5 mg | Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP]) | Change from Baseline at Day 14 | -0.74 score on scale | Standard Deviation 0.86 |
| Placebo 7.5 mg | Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP]) | Baseline | 5.62 score on scale | Standard Deviation 1.78 |
| Placebo 7.5 mg | Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP]) | Change from Baseline at Day 14 | -0.23 score on scale | Standard Deviation 0.83 |
| Placebo 7.5 mg | Disease Activity Score 28 (DAS28) (C-reactive Protein [CRP]) | Day 14 | 5.38 score on scale | Standard Deviation 1.6 |