Combination Antibiotic Treatment for Reactive Arthritis Caused by Chlamydia Bacteria - Full Text View

Sponsored by:	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by:	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ClinicalTrials.gov Identifier:	NCT00351273

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 III

MedlinePlus related topics: Antibiotics Chlamydia Infections

Drug Information available for: Azithromycin Doxycycline Doxycycline calcium Doxycycline hyclate Rifampin Methylcellulose

U.S. FDA Resources

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

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
1: Active Comparator 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)
2: Active Comparator Participants will receive Doxycycline and Rifampin	Drug: Doxycycline and Rifampin doxycycline 100mg daily; rifampin 300mg daily (both for 6 months)
3: Placebo Comparator 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

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

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

Principal Investigator:

John D. Carter, MD

University of South Florida

More Information

Publications:

Carter JD, Valeriano J, Vasey FB. Doxycycline versus doxycycline and rifampin in undifferentiated spondyloarthropathy, with special reference to chlamydia-induced arthritis. A prospective, randomized 9-month comparison. J Rheumatol. 2004 Oct;31(10):1973-80.

Responsible Party:	University of South Florida ( John D. Carter, M.D./Principal Investigator )
Study ID Numbers:	R21 AR053646, 1R21AR053646-01
Study First Received:	July 10, 2006
Last Updated:	September 19, 2008
ClinicalTrials.gov Identifier:	NCT00351273
Health Authority:	United States: Federal Government

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

Chlamydia

Study placed in the following topic categories:

Spinal Diseases
Joint Diseases
Spondylarthropathy
Arthritis, Infectious
Arthritis, Reactive
Bone Diseases
Rifampin
Musculoskeletal Diseases

Arthritis
Azithromycin
Chlamydia Infections
Reiter's Syndrome
Spondylarthritis
Doxycycline
Spondylarthropathies

Additional relevant MeSH terms:

Anti-Infective Agents
Antiprotozoal Agents
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection
Pharmacologic Actions
Antibiotics, Antitubercular

Anti-Bacterial Agents
Antimalarials
Antiparasitic Agents
Therapeutic Uses
Antitubercular Agents
Nucleic Acid Synthesis Inhibitors
Leprostatic Agents

ClinicalTrials.gov processed this record on January 14, 2009