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Combination Antibiotic Treatment for Reactive Arthritis Caused by Chlamydia Bacteria

This study has been completed.
Sponsor:
Information provided by:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ClinicalTrials.gov Identifier:
NCT00351273
First received: July 10, 2006
Last updated: January 29, 2009
Last verified: January 2009
  Purpose

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.


Condition Intervention Phase
Arthritis, Reactive
Reiter Disease
Drug: Doxycycline and Rifampin
Drug: Azithromycin and Rifampin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 3 Trial to Assess the Efficacy of Long-Term (6 Months) Combination Antibiotics as a Treatment for Chlamydia-Induced Reactive Arthritis

Resource links provided by NLM:


Further study details as provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):

Primary Outcome Measures:
  • Number of responders in the combination antimicrobial groups versus number of responders in the placebo group [ Time Frame: Month 6 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Individual comparison of 6 "responder" criteria in the combination antimicrobial groups versus the placebo group [ Time Frame: Months 6 and 9 ] [ Designated as safety issue: No ]
  • Comparison of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
  • Psoriatic Arthritis Response Criteria (PsARC): swollen joint count, tender joint count, physician and patient global assessment [ Time Frame: Months 6 and 9 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Dactylitis [ Time Frame: Months 6 and 9 ] [ Designated as safety issue: No ]
  • Enthesitis (presence or absence of plantar fasciitis or Achilles tendonitis) [ Time Frame: Months 6 and 9 ] [ Designated as safety issue: No ]
  • Health Assessment Questionnaire (HAQ) [ Time Frame: Months 6 and 9 ] [ Designated as safety issue: No ]
  • Number of patients with a complete response (resolution of all symptoms) [ Time Frame: Months 1, 3, 6 and 9 ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: May 2006
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Participants will receive Azithromycin and Rifampin
Drug: Azithromycin and Rifampin
Azithromycin 500mg daily for 5 days and then twice weekly; Rifampin 300mg daily (both for 6 months)
Active Comparator: 2
Participants will receive Doxycycline and Rifampin
Drug: Doxycycline and Rifampin
doxycycline 100mg daily; rifampin 300mg daily (both for 6 months)
Placebo Comparator: 3
Participants will receive placebo
Drug: Placebo
Methylcellulose

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meet the following European Spondyloarthropathy Study Group Criteria:

    1. inflammatory spinal pain OR
    2. synovitis AND
    3. one or more of the following:

      1. positive family history
      2. urethritis or cervicitis within 1 month prior to onset of arthritis
      3. buttock pain
      4. enthesopathy
      5. sacroiliitis
  • Disease duration of at least 6 months
  • Negative pregnancy test at study baseline and willing to use an effective method of contraception other than combined oral contraceptives for the duration of the study (for women of childbearing age)

Exclusion Criteria:

  • Sensitivity or history of allergic reaction to rifampin, doxycycline, or azithromycin
  • Currently taking any medications that may interact with the study medications, specifically rifampin
  • Liver transaminases greater than or equal to two times the normal level
  • Significant abnormalities in the complete blood count (CBC)
  • Pregnant
  • Current psoriasis
  • Diagnosis of inflammatory bowel disease
  • Diagnosis of ankylosing spondylitis
  • Previous prolonged exposure to antibiotics (more than 2 weeks) as a potential treatment for reactive arthritis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00351273

Locations
United States, Florida
University of South Florida
Tampa, Florida, United States, 33612
United States, Louisiana
Louisiana State University
New Orleans, Louisiana, United States, 70112
Canada, Ontario
University of Toronto
Toronto, Ontario, Canada, M5T 2S8
Sponsors and Collaborators
Investigators
Principal Investigator: John D. Carter, MD University of South Florida
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: John D. Carter, M.D./Principal Investigator, University of South Florida
ClinicalTrials.gov Identifier: NCT00351273     History of Changes
Other Study ID Numbers: R21 AR053646, 1R21AR053646-01
Study First Received: July 10, 2006
Last Updated: January 29, 2009
Health Authority: United States: Federal Government

Keywords provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):
Chlamydia

Additional relevant MeSH terms:
Arthritis
Arthritis, Reactive
Arthritis, Infectious
Bone Diseases
Infection
Joint Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthritis
Spondylarthropathies
Spondylitis
Doxycycline
Rifampin
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antitubercular
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Antitubercular Agents
Enzyme Inhibitors
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014