Combination Antibiotic Treatment for Reactive Arthritis Caused by Chlamydia Bacteria

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00351273
Recruitment Status : Completed
First Posted : July 12, 2006
Results First Posted : August 10, 2016
Last Update Posted : November 12, 2018
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
University of South Florida

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.

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

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, 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
Study Start Date : May 2006
Actual Primary Completion Date : September 2008
Actual Study Completion Date : September 2008

Arm Intervention/treatment
Active Comparator: Azithromycin and Rifampin
Participants received Azithromycin and Rifampin
Drug: Azithromycin and Rifampin
Azithromycin 500mg daily for 5 days and then twice weekly; Rifampin 300mg daily (both for 6 months)
Other Name: Zithromax and Rifadin

Active Comparator: Doxycycline and Rifampin
Participants received Doxycycline and Rifampin
Drug: Doxycycline and Rifampin
doxycycline 100mg daily; rifampin 300mg daily (both for 6 months)
Other Name: Atridox and Rifadin

Placebo Comparator: received placebo
Participants received placebo
Drug: Placebo
Other Name: Placebo effect

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Number of Patients With a Complete Response (Resolution of All Symptoms) [ Time Frame: Months 6 and 9 ]
    Patients who completed full 6 months of treatment that reported feeling complete resolution of symptoms at month 6 visit and had no worsening of condition at the month 9 follow up visit.

  2. Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Baseline Month 1, 3, 6 and 9 ]
    Comparison of mean ESR rates of combination antibiotic group vs placebo group at Baseline, Month 1, 3, 6 and 9

  3. hsCRP [ Time Frame: Baseline, Month 1, 3, and 6 ]
    Comparison of high sensitivity C-reactive protein measurement in combination antibiotic group vs placebo group at Baseline, Month 1, 3, and 6

  4. HAQ DI Score [ Time Frame: Baseline, Month 1,3,6 and 9 ]

    Comparison of HAQ-DI score of combination antibiotic group vs placebo group at Baseline, Month 1,3,6 and 9 The Health assessment questionnaire disability index (HAQ-DI) is a questionnaire for the assessment of Rheumatoid Arthritis. The questionnaire is a patient reported outcome (PRO) which is usually self-administered by the patient There are 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are 2 or 3 questions for each section. Scoring within each section is from 0 (without any difficulty) to 3 (unable to do). For each section the score given to that section is the worst score within the section, i.e. if one question is scored 1 and another 2, then the score for the section is 2. In addition, if an aide or device is used or if help is required from another individual, then the minimum score for that section is 2. If the section score is already 2 or more then no modification is made.

    The 8 scores of the 8 sections are summed and divided

  5. PhGA Assessment [ Time Frame: Baseline, month 1,3,6 and 9 ]
    Comparison of Physician's global assessment of disease activity (PhGA) using 0-100mm visual analog scale (VAS) , where 0 indicates the best possible outcome and 100 indicates the worst possible outcome, in combination antibiotic vs placebo groups at Baseline, month 1,3,6 and 9

  6. Swollen 76 Joint Count (SJC) [ Time Frame: Baseline, month 1,3,6 and 9 ]
    Comparison of modified Swollen Joint Counts between combination antibiotic and placebo groups at Baseline, Month 1, 3, 6 and 9. Determination of swelling in each of the 76 joints was determined by any swelling or absence of swelling. Each swollen joint receives a value of 1, ranging from 0-76 as a possible score.

  7. 78 Tender Joint Count (TJC) [ Time Frame: Baseline, Month 1, 3, 6 and 9 ]
    Comparison of modified 78 Tender Joint Count (TJC) between combination antibiotic and placebo groups at Baseline, Month 1, 3, 6 and 9. Determination of tender joing in each of the 78 joints was determined by examination. Each tender joint receives a value of 1, ranging from 0-78 as a possible score.

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00351273

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
University of South Florida
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Principal Investigator: John D. Carter, MD University of South Florida

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: University of South Florida Identifier: NCT00351273     History of Changes
Other Study ID Numbers: R21AR053646 ( U.S. NIH Grant/Contract )
R21AR053646 ( U.S. NIH Grant/Contract )
1R21AR053646-01 ( U.S. NIH Grant/Contract )
First Posted: July 12, 2006    Key Record Dates
Results First Posted: August 10, 2016
Last Update Posted: November 12, 2018
Last Verified: June 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University of South Florida:

Additional relevant MeSH terms:
Chlamydia Infections
Arthritis, Reactive
Joint Diseases
Musculoskeletal Diseases
Chlamydiaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Sexually Transmitted Diseases, Bacterial
Sexually Transmitted Diseases
Genital Diseases, Male
Genital Diseases, Female
Arthritis, Infectious
Spinal Diseases
Bone Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors