Combination Antibiotic Treatment for Reactive Arthritis Caused by Chlamydia Bacteria

Study Overview
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Brief Summary
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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 Description
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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.

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

Conditions
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Arthritis, Reactive, Reiter Disease

Intervention / Treatment
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* Drug: Doxycycline and Rifampin
* Drug: Azithromycin and Rifampin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the following European Spondyloarthropathy Study Group Criteria: inflammatory spinal pain OR synovitis AND one or more of the following: positive family history urethritis or cervicitis within 1 month prior to onset of arthritis buttock pain enthesopathy 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Azithromycin and Rifampin<br>Participants received Azithromycin and Rifampin | Drug: Azithromycin and Rifampin<br>* Azithromycin 500mg daily for 5 days and then twice weekly; Rifampin 300mg daily (both for 6 months)<br>* Other names: Zithromax and Rifadin;|
| Active Comparator: Doxycycline and Rifampin<br>Participants received Doxycycline and Rifampin | Drug: Doxycycline and Rifampin<br>* doxycycline 100mg daily; rifampin 300mg daily (both for 6 months)<br>* Other names: Atridox and Rifadin;|
| Placebo Comparator: received placebo<br>Participants received placebo | Drug: Placebo<br>* Methylcellulose<br>* Other names: Placebo effect;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate Whether a 6 Month Course of Combined Antibiotics Was Effective Treatment. | 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. | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With a Complete Response (Resolution of All Symptoms) | 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. | Months 6 and 9 | 
| Erythrocyte Sedimentation Rate (ESR) | Comparison of mean ESR rates of combination antibiotic group vs placebo group at Baseline, Month 1, 3, 6 and 9 | Baseline Month 1, 3, 6 and 9 | 
| hsCRP | Comparison of high sensitivity C-reactive protein measurement in combination antibiotic group vs placebo group at Baseline, Month 1, 3, and 6 | Baseline, Month 1, 3, and 6 | 
| HAQ DI Score | 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 | Baseline, Month 1,3,6 and 9 | 
| PhGA Assessment | 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 | Baseline, month 1,3,6 and 9 | 
| Swollen 76 Joint Count (SJC) | 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. | Baseline, month 1,3,6 and 9 | 
| 78 Tender Joint Count (TJC) | 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. | Baseline, Month 1, 3, 6 and 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chlamydia