A Study of the Effects of Oral Prednisone in Patients With Rheumatoid Arthritis (MK0000-088)

A Randomized, Double-Blind, Parallel Group, Placebo Controlled Study to Access the Effects of Oral Prednisone on Clinical Efficacy and the Power Doppler Ultrasound Signal of Synovium in Patients With Rheumatoid Arthritis

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Prednisone 15 mg; Drug: Placebo Tablets; Drug: Prednisone 7.5 mg; Drug: Placebo Over-Encapsulated Tablets

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prednisone 15 mg; Prednisone 15 mg tablets once daily for 15 days	Drug: Prednisone 15 mg; Prednisone 15 mg tablets once daily for 15 days.; Other Names: Prednisone
Placebo Comparator: Placebo 15 mg; Prednisone 15 mg placebo tablets once daily for 15 days	Drug: Placebo Tablets; Prednisone placebo tablets once daily for 15 days.
Experimental: 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.	Drug: Prednisone 7.5 mg; Prednisone 7.5 mg over-encapsulated tablets once daily for 15 days; Other Names: Prednisone
Placebo Comparator: 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.	Drug: Placebo Over-Encapsulated Tablets; Prednisone 7.5 mg placebo over-encapsulated tablets once daily for 15 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and Day 14

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Seymour MW, Kelly S, Beals CR, Malice MP, Bolognese JA, Dardzinski BJ, Cheng AS, Cummings CE, Smugar SS, McClinton C, Fox A, Dooley WM, Pitzalis C, Taylor PC. Ultrasound of metacarpophalangeal joints is a sensitive and reliable endpoint for drug therapies in rheumatoid arthritis: results of a randomized, two-center placebo-controlled study. Arthritis Res Ther. 2012 Sep 12;14(5):R198. doi: 10.1186/ar4034.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: September 3, 2008
• First Submitted That Met QC Criteria: September 3, 2008
• First Posted (Estimate): September 4, 2008

Study Record Updates

• Last Update Posted (Estimate): May 29, 2015
• Last Update Submitted That Met QC Criteria: May 7, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: 0000-088; 2008_531