Arthritis, ReactivePhase 3NCT00351273
Combination Antibiotic Treatment for Reactive Arthritis Caused by Chlamydia Bacteria
A Phase 3 study testing Doxycycline and Rifampin and Azithromycin and Rifampin in people with Arthritis, Reactive and Reiter Disease, run by University of South Florida at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Arthritis, Reactive, Reiter Disease
- What is being tested?
- Doxycycline and Rifampin and Azithromycin and Rifampin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 3 sitesin 2 countries
- Study dates
- May 2006to Sep 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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)
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Louisiana State University
New Orleans, Louisiana, 70112
University of South Florida
Tampa, Florida, 33612
About this 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
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.
Read the 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.
- Conditions
- Arthritis, Reactive, Reiter Disease
- Being tested
- Doxycycline and Rifampin, Azithromycin and Rifampin, Placebo
- Keywords
- Chlamydia
- Medical subject headings
- Arthritis, Reactive, Chlamydia Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Doxycycline and RifampinDrug
Also called Atridox and Rifadin
doxycycline 100mg daily; rifampin 300mg daily (both for 6 months)
Azithromycin and RifampinDrug
Also called Zithromax and Rifadin
Azithromycin 500mg daily for 5 days and then twice weekly; Rifampin 300mg daily (both for 6 months)
PlaceboDrug
Also called Placebo effect
Methylcellulose
| Study group | Role | What they receive |
|---|---|---|
| Azithromycin and Rifampin | Active comparator | Participants received Azithromycin and Rifampin Receives: Drug: Azithromycin and Rifampin |
| Doxycycline and Rifampin | Active comparator | Participants received Doxycycline and Rifampin Receives: Drug: Doxycycline and Rifampin |
| received placebo | Placebo comparator | Participants received placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Month 6
Secondary outcomes (7)
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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: Baseline, Month 1, 3, 6 and 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2006 (estimated)
- Study startMay 2006
- Primary completionSep 2008
- Study completionSep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Arthritis, ReactiveStudies of the same condition, open and under way.
- More trials run by University of South FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of South Florida
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Sponsor
- Investigators
- John D. Carter, MD, Principal investigator, University of South Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00351273
- Sponsor's protocol ID
- R21AR053646
- Other IDs
- R21AR053646, 1R21AR053646-01
- Status last verified
- Jun 2016
- First submitted
- 10 Jul 2006
- Last updated
- 13 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
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.
PubMed 15468362Carter JD, Espinoza LR, Inman RD, Sneed KB, Ricca LR, Vasey FB, Valeriano J, Stanich JA, Oszust C, Gerard HC, Hudson AP. Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis: a double-blind, placebo-controlled, prospective trial. Arthritis Rheum. 2010 May;62(5):1298-307. doi: 10.1002/art.27394.
PubMed 20155838
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3 Trial to Assess the Efficacy of Long-term (6 Months) Combination Antibiotics as a Treatment for Chlamydia-induced Reactive Arthritis
- ClinicalTrials.gov ID
- NCT00351273
- Acronym / sponsor ID
- R21AR053646
- Conditions
- Arthritis, Reactive, Reiter Disease
- Keywords
- Chlamydia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University of South FloridaUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- May 2006
- Primary completion
- Sep 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 12 Jul 2006 (estimated)
- Results
- Posted 10 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Azithromycin and Rifampin | Active comparator | Drug: Azithromycin and RifampinParticipants received Azithromycin and Rifampin |
| Doxycycline and Rifampin | Active comparator | Drug: Doxycycline and RifampinParticipants received Doxycycline and Rifampin |
| received placebo | Placebo comparator | Drug: PlaceboParticipants received placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Meet the following European Spondyloarthropathy Study Group Criteria:
- 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)
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Doxycycline and RifampinAlso: Atridox and Rifadindoxycycline 100mg daily; rifampin 300mg daily (both for 6 months) | Drug | Doxycycline and Rifampin |
| Azithromycin and RifampinAlso: Zithromax and RifadinAzithromycin 500mg daily for 5 days and then twice weekly; Rifampin 300mg daily (both for 6 months) | Drug | Azithromycin and Rifampin |
| PlaceboAlso: Placebo effectMethylcellulose | Drug | received placebo |
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.
7 secondary outcomes
Number of Patients With a Complete Response (Resolution of All Symptoms)
Time frame: Months 6 and 9
Erythrocyte Sedimentation Rate (ESR)
Time frame: Baseline Month 1, 3, 6 and 9
hsCRP
Time frame: Baseline, Month 1, 3, and 6
HAQ DI Score
Time frame: Baseline, Month 1,3,6 and 9
PhGA Assessment
Time frame: Baseline, month 1,3,6 and 9
Swollen 76 Joint Count (SJC)
Time frame: Baseline, month 1,3,6 and 9
78 Tender Joint Count (TJC)
Time frame: Baseline, Month 1, 3, 6 and 9
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15468362Carter 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.
- Derived from this study: PubMed 20155838Carter JD, Espinoza LR, Inman RD, Sneed KB, Ricca LR, Vasey FB, Valeriano J, Stanich JA, Oszust C, Gerard HC, Hudson AP. Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis: a double-blind, placebo-controlled, prospective trial. Arthritis Rheum. 2010 May;62(5):1298-307. doi: 10.1002/art.27394.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John D. Carter, MD principal investigator
University of South Florida
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Doxycycline and Rifampin and Azithromycin and Rifampin in people with Arthritis, Reactive and Reiter Disease, run by University of South Florida at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Investigate Whether a 6 Month Course of Combined Antibiotics Was Effective Treatment. (time frame: Month 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00351273, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2018.