Clinical Trial: Combination Antibiotic Treatment for Reactive Arthritis Caused by Chlamydia Bacteria

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase 3 Trial to Assess the Efficacy of Long-term (6 Months) Combination Antibiotics as a Treatment for Chlamydia-induced Reactive Arthritis

Brief Summary: Reactive arthritis, also known as Reiter's syndrome, is a form of arthritis that occurs as a reaction to an infection elsewhere in the body. It is characterized by inflammation of the joints, tendons, urogenital tract, and eyes. Pain and swelling in the knees, ankles, and feet are common. This study will determine the effectiveness of antibiotic therapy in treating people with chlamydia-induced reactive arthritis that has lasted for more than 6 months.

Detailed Summary:

The initial infection that causes reactive arthritis is caused by one of two bacteria: Chlamydia trachomatis, which is usually acquired through sexual contact, or Chlamydia pneumoniae, which can cause respiratory infections. Most people recover fully from the initial flare of arthritis symptoms. However, about 20% of people with reactive arthritis experience long-lasting symptoms. In these individuals, the Chlamydia bacteria exist in a persistent metabolically active state within the joint tissue, even years after the initial exposure. The bacteria produce heat shock proteins (HSPs), which are thought to play a key role in the chronic persistent state of Chlamydia and which may stimulate the immune inflammatory response seen in reactive arthritis. This indicates the need for antimicrobial therapy that can reduce Chlamydia's HSP production and block its metabolism. The purpose of this study is to determine the effectiveness of long-term combination antibiotic therapy in treating people with chronic reactive arthritis. The study will use two different combinations of common antibiotics: doxycycline paired with rifampin and azithromycin paired with rifampin.

This study will entail 6 months of treatment followed by 3 months of follow-up. After screening, eligible participants will be randomly assigned to one of three treatment groups: rifampin once a day plus doxycycline twice a day; rifampin once a day plus azithromycin once a day for 5 days, then twice weekly; or placebo. Study visits will occur at baseline and Months 1, 3, 6, and 9. At all visits, participants will undergo an interview, a physical examination, and blood collection. They will also complete a questionnaire related to their symptoms and functional status. At screening and Month 6, a synovial biopsy may be performed. This will involve taking a sample of the tissue that lines the joints.


Sponsor: University of South Florida

Current Primary Outcome: Investigate Whether a 6 Month Course of Combined Antibiotics Was Effective Treatment. [ Time Frame: Month 6 ]

The outcome measure was a composite endpoint. Participants had to meet 4/6 clinical criteria. 17/24 subjects randomized to combination antibiotics did respond to treatment when compared to 3/10 randomized to placebo.


Original Primary Outcome:

  • number of responders in the combination antimicrobial groups versus number of responders in the placebo group (measured at Month 6)
  • "responder" defined as 20% or more improvement in at least 4 of 6 criteria: 1) swollen joint count, 2) tender joint count, 3) morning stiffness duration (low back), 4) current low back pain, 5) current peripheral joint pain, 6) patient global assessment


Current Secondary Outcome:

  • Individual Comparison of 6 "Responder" Criteria in the Combination Antimicrobial Groups Versus the Placebo Group [ Time Frame: Months 6 and 9 ]
  • Comparison of Erythrocyte Sedimentation Rate (ESR) and C-reactive Protein (CRP) [ Time Frame: Month 6 ]
  • Psoriatic Arthritis Response Criteria (PsARC): Swollen Joint Count, Tender Joint Count, Physician and Patient Global Assessment [ Time Frame: Months 6 and 9 ]
  • Disease Activity Score 44 (DAS44): Ritchie Articular Index (Tender Joint Count), Swollen Joint Count (Out of 44 Joints), ESR, Patient Global Assessment (Visual Analog Scale) [ Time Frame: Months 6 and 9 ]
  • Dactylitis [ Time Frame: Months 6 and 9 ]
  • Enthesitis (Presence or Absence of Plantar Fasciitis or Achilles Tendonitis) [ Time Frame: Months 6 and 9 ]
  • Health Assessment Questionnaire (HAQ) [ Time Frame: Months 6 and 9 ]
  • Number of Patients With a Complete Response (Resolution of All Symptoms) [ Time Frame: Months 1, 3, 6 and 9 ]


Original Secondary Outcome:

  • individual comparison of above 6 criteria in the combination antimicrobial groups versus the placebo group
  • Comparison of Erythrocyte Sedimentation Rate (ESR) and C-reactive Protein (CRP)
  • Psoriatic Arthritis Response Criteria (PsARC): Swollen Joint Count, Tender Joint Count, Physician and Patient Global Assessment
  • Disease Activity Score 44 (DAS44): Ritchie Articular Index (Tender Joint Count), Swollen Joint Count (Out of 44 Joints), ESR, Patient Global Assessment (Visual Analog Scale)
  • Dactylitis
  • Enthesitis (Presence or Absence of Plantar Fasciitis or Achilles Tendonitis)
  • Health Assessment Questionnaire (HAQ)
  • number of patients with a complete response (resolution of all symptoms) (all measured at Months 1, 3, 6, and 9)


Information By: University of South Florida

Dates:
Date Received: July 10, 2006
Date Started: May 2006
Date Completion:
Last Updated: August 10, 2016
Last Verified: June 2016