<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02242474</url>
  </required_header>
  <id_info>
    <org_study_id>1-levallee</org_study_id>
    <nct_id>NCT02242474</nct_id>
  </id_info>
  <brief_title>Anti-TNFα Use During Elective Foot and Ankle Surgery in Patients With Rheumatoid Arthritis</brief_title>
  <official_title>Prospective Randomized Multicentric Trial on Anti-TNFα Treatment and Infection Risk in the Perioperative Period During Elective Foot and Ankle Surgery in Patients With Rheumatoid Arthritis.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CHU de Quebec-Universite Laval</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CHU de Quebec-Universite Laval</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rheumatoid arthritis (RA) is a frequent inflammatory arthritis that can lead to severe joint&#xD;
      deformity and often requires orthopaedic surgical interventions. Anti-Tumor Necrosis Factor α&#xD;
      (anti-TNFα) are biological disease-modifying antirheumatic drugs (DMARDs) increasingly used&#xD;
      in the treatment of rheumatoid arthritis. An increased risk of opportunistic infection was&#xD;
      demonstrated in patients treated with those drugs. This observation led many national&#xD;
      committees to recommend anti-TNFα suspension in the perioperative period to avoid a raise in&#xD;
      the postoperative infection risk in those patients. This approach is not supported by the&#xD;
      data available in the current literature and it exposes patients to an increased risk of&#xD;
      inflammatory flare ups of their disease during and after anti-TNFα suspension, which can&#xD;
      compromise their postoperative rehabilitation and their quality of life.&#xD;
&#xD;
      The objective of this prospective randomized multicentric trial is to determine the effect of&#xD;
      anti-TNFα suspension in the perioperative period on the postoperative infection risk.&#xD;
      Overall, 660 rheumatoid arthritis patients requiring an elective foot or ankle surgery will&#xD;
      be randomized into two groups. In the first group, anti-TNFα will be stopped 3 half-lives&#xD;
      before the surgery while they will be continued in the second group. The postoperative&#xD;
      infection rate will be compared between the two groups. Postoperative complication rates,&#xD;
      flares and revision surgeries as well as the functional improvement will be compared.&#xD;
&#xD;
      The study hypothesis is that there is no significant difference in the risk of postoperative&#xD;
      infection between the two groups.&#xD;
&#xD;
      Results from this study will help determine the optimal way to use anti-TNFα in the&#xD;
      perioperative period and will therefore improve the quality of life of rheumatoid arthritis&#xD;
      patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A. STUDY DESIGN This is a prospective randomized multicentric trial. Patients will be&#xD;
      randomized into two groups. Patients in Group A will continue their anti-TNF treatment during&#xD;
      the whole perioperative period. Anti-TNFα medication will be suspended prior to the surgery&#xD;
      in patients randomized in Group B. This design will allow us to minimize the important&#xD;
      selection bias that was affecting the observational studies previously conducted on this&#xD;
      topic. Due to safety concerns, patients and evaluators will not be blinded to the treatment.&#xD;
&#xD;
      B. RESEARCH LOCATION Considering the important number of patients required, we plan on&#xD;
      conducting a multicentric study. This will allow us to recruit enough patients in a&#xD;
      reasonable time frame to ensure sufficient power to our results. The main center where the&#xD;
      data will be gathered is the CHU de Québec. Other centers in Canada will be invited to&#xD;
      participate in the study for a maximum of 10 centers.&#xD;
&#xD;
      C. INTERVENTION Medication Patients randomized to Group A will continue their anti-TNFα&#xD;
      treatment unaltered during the whole perioperative period. Surgery will be performed without&#xD;
      consideration in regards to the timing of the treatment. The time elapsed between the last&#xD;
      anti-TNFα administration and the surgery will nonetheless be documented.&#xD;
&#xD;
      Patients randomized to Group B will have their anti-TNFα therapy interrupted before surgery.&#xD;
      There is no consensus on the optimal timing of anti-TNFα suspension before surgery. Many&#xD;
      published guidelines suggest that the pharmacokinetics of the different anti-TNFα medications&#xD;
      should be an important consideration in the perioperative management of these drugs.&#xD;
      Different authors suggested that anti-TNFα therapies should be suspended between two and five&#xD;
      half-lives prior to surgery. Similar timing was used in previous publications. In the current&#xD;
      trial, anti-TNFα will be suspended three half-lives (± seven days) prior to surgery. All&#xD;
      other medications used in the treatment of the disease (methotrexate, hydroxychloroquine,&#xD;
      corticosteroid, etc.) will be documented and continued in the perioperative period.&#xD;
      Non-steroidal anti-inflammatory drugs (NSAID) will be suspended seven days prior to surgery&#xD;
      and will be restarted postoperatively. Anti-TNFα will be restarted once wound healing is&#xD;
      completed.&#xD;
&#xD;
      Surgery&#xD;
&#xD;
      All surgeries will be performed by experimented orthopaedic surgeons. Surgical techniques&#xD;
      will be determined by the treating surgeon and will not be subject to randomization. For&#xD;
      analysis purposes, surgeries will be subdivided in surgeries with and without permanent&#xD;
      implants. It will also be divided between forefoot, midfoot, hindfoot and ankle surgeries.&#xD;
      Use of prophylactic antibiotics will be standardized as follow:&#xD;
&#xD;
        -  Cephalexin 2g IV before the incision or,&#xD;
&#xD;
        -  Clindamycin 600mg IV before the incision if patient is allergic to cephalexin D.&#xD;
           RANDOMIZATION Randomization will be completed as soon as the inclusion and exclusion&#xD;
           criteria are verified and the patient has given informed consent. Patients will be&#xD;
           randomized to treatment Group A or B. Randomization will be performed in blocks of 10&#xD;
           using the web site Randomizer.org. Blocks of 10 numbered, sealed and opaque envelopes&#xD;
           will be sent to the participating centers.&#xD;
&#xD;
      E. FOLLOW-UP SCHEDULE Patients will be followed for one year after surgery. There is going to&#xD;
      be one visit before surgery and five follow-up visits at two weeks, six week, three months,&#xD;
      six months and 12 months after surgery.&#xD;
&#xD;
      F. SAMPLE SIZE CALCULATION We calculated the sample size needed to test for equivalence&#xD;
      between the two groups with a statistical power of 80% and a type I error (alpha) of 5%. The&#xD;
      observed rate of infection following foot and ankle surgery in RA patient varies greatly in&#xD;
      the literature [46]. For the purpose of the sample size calculation, we used a 5% rate of&#xD;
      infection and considered a relative risk of 2 to be clinically significant.&#xD;
&#xD;
      N1 = N2 = 2*((1.96+0.845)/0.05)^2*0.05*(1-0.05) = 299&#xD;
&#xD;
      Considering a rate of lost to follow-up of 15%, we concluded that a sample of 660 patients,&#xD;
      330 in each treatment group, would provide us relevant results.&#xD;
&#xD;
      G. STATISTICAL ANALYSIS Descriptive analysis Demographic data and baseline clinical&#xD;
      characteristics obtained will be analyzed. For each continuous variable, the mean, the&#xD;
      median, the standard deviation as well as the maximum and minimum values are going to be&#xD;
      presented for each group. For categorical variable, the frequencies and proportions are going&#xD;
      to be presented. All these variables are going to be compared between the two groups using&#xD;
      Student's T-test for continuous variables and the Chi-squared test for categorical variables.&#xD;
&#xD;
      Main analysis The main outcome analysis is going to be made using the Chi-squared test. The&#xD;
      gross surgical site infection (SSI) relative risk between the two groups will be calculated.&#xD;
      The relative risk will also be adjusted using a multivariate regression analysis that will&#xD;
      consider relevant demographic variables. The model will include, but will not be limited, to&#xD;
      the variables that are statistically different between the two groups. Secondary outcomes&#xD;
      related to disease flare up, poor wound healing and reoperation rate will also be analyzed&#xD;
      using Chi-squared test. A linear regression model with repeated measures will be used to&#xD;
      compare functional scores improvements between the two groups.&#xD;
&#xD;
      Sub-group analysis will be performed. They will include analysis by type of surgery, by use&#xD;
      of permanent implants, by baseline disease activity level and by type of anti-TNFα used.&#xD;
&#xD;
      Interim analysis An interim analysis will be performed at the midpoint of the recruitment&#xD;
      period to look for a significant difference in the primary outcome between the two groups.&#xD;
      The analysis will take place when 330 patients will have been followed for at least six weeks&#xD;
      after surgery. Based on the obtained results, a decision to interrupt the trial could&#xD;
      eventually be made by the safety committee.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>July 2015</start_date>
  <completion_date type="Anticipated">October 2019</completion_date>
  <primary_completion_date type="Anticipated">October 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Surgical site infection</measure>
    <time_frame>Within one year after surgery</time_frame>
    <description>Surgical site infection will be determined according to the definition of the Center for Disease Control (CDC).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease flare up</measure>
    <time_frame>From the time the drug is suspended until one year after surgery</time_frame>
    <description>There is currently no widely accepted definition of RA disease flare up. In this study, patients satisfying one of the two following criteria will be considered as having a disease flare up:&#xD;
I. Modification of the medication made necessary by an increase in the disease symptoms.&#xD;
II. Increase in disease activity according to the Clinical Disease Activity Index (CDAI):&#xD;
Increase from a remission or a low disease activity level at baseline to a moderate or high activity level.&#xD;
or&#xD;
Increase from a moderate disease activity level at baseline to a high activity level.&#xD;
or&#xD;
An increase of 12 points or more on the CDAI in patients having a high disease activity level at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in functional level</measure>
    <time_frame>Until one year after surgery</time_frame>
    <description>The functional level of each patient is going to be assessed using the Health Assessment Questionnaire (HAQ) before and after the surgery in accordance with the follow-up schedule presented in the protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Poor wound healing</measure>
    <time_frame>Within one year of surgery or until wound is completely healed</time_frame>
    <description>Complications associated with poor wound healing such as delayed wound healing and dehiscence will be noted. Delayed wound healing will be defined as a wound that isn't completely healed 14 days after surgery. Dehiscence will be defined as a wound that requires secondary closure or a wound that heals by secondary intention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reoperation rate</measure>
    <time_frame>Within one year of surgery</time_frame>
    <description>All reoperations made necessary following postoperative complications (ex : infection, implant retrieval, debridement) will be documented. More than one reoperation can be performed for the same patient. The reoperation rate expressed as a percentage will be compared between the two groups.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Other adverse events</measure>
    <time_frame>Within one year of surgery</time_frame>
    <description>All other significant adverse events will be documented. For example, systemic infection, septic choc, implant loosening and arthrodesis nonunion are going to be noted. Nonunion is going to be defined as the persistence of a joint space on more than 50% of the articular surface visible on CT-Scan six months after surgery associated with pain.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">660</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>Anti-TNF suspended perioperatively</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomized to Group B will have their anti-TNFα therapy interrupted before surgery. Different authors suggested that anti-TNFα therapies should be suspended between two and five half-lives prior to surgery. In the current trial, anti-TNFα will be suspended three half-lives (± seven days) prior to surgery. All other medications used in the treatment of the disease (methotrexate, hydroxychloroquine, corticosteroid, etc.) will be documented and continued in the perioperative period. Non-steroidal anti-inflammatory drugs (NSAID) will be suspended seven days prior to surgery and will be restarted postoperatively. Anti-TNFα will be restarted once wound healing is completed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anti-TNFα continued perioperatively</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to Group A will continue their anti-TNFα treatment unaltered during the whole perioperative period. Surgery will be performed without consideration in regards to the timing of the treatment. The time elapsed between the last anti-TNFα administration and the surgery will nonetheless be documented.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anti-TNF suspended perioperatively</intervention_name>
    <arm_group_label>Anti-TNF suspended perioperatively</arm_group_label>
    <other_name>Infliximab</other_name>
    <other_name>Remicade</other_name>
    <other_name>Etanercept</other_name>
    <other_name>Enbrel</other_name>
    <other_name>Adalimumab</other_name>
    <other_name>Humira</other_name>
    <other_name>Certolizumab</other_name>
    <other_name>Cimzia</other_name>
    <other_name>Golimumab</other_name>
    <other_name>Simponi</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anti-TNFα continued perioperatively</intervention_name>
    <arm_group_label>Anti-TNFα continued perioperatively</arm_group_label>
    <other_name>Infliximab</other_name>
    <other_name>Remicade</other_name>
    <other_name>Etanercept</other_name>
    <other_name>Enbrel</other_name>
    <other_name>Adalimumab</other_name>
    <other_name>Humira</other_name>
    <other_name>Certolizumab</other_name>
    <other_name>Cimzia</other_name>
    <other_name>Golimumab</other_name>
    <other_name>Simponi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female 18 years of age or older&#xD;
&#xD;
          -  Rheumatoid arthritis diagnostic according to the American College Rheumatology (ACR)&#xD;
             1987 criteria [38]&#xD;
&#xD;
          -  Patient treated with anti-TNFα for at least six months&#xD;
&#xD;
          -  Elective unilateral surgery of the foot and ankle&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient unable to give informed consent&#xD;
&#xD;
          -  Surgery on an infected site&#xD;
&#xD;
          -  Severe distal peripheral vascular disease (no distal pulse)&#xD;
&#xD;
          -  Medical condition contraindicating surgery&#xD;
&#xD;
          -  Patient treated with biologic DMARD other than anti-TNFα&#xD;
&#xD;
          -  Circumstances preventing an adequate postoperative follow-up&#xD;
&#xD;
          -  Revision surgery&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mélissa Laflamme, MD, MsC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Hôspitalier Universitaire de Québec</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Melissa Laflamme, MD, MSc</last_name>
    <phone>418-525-4444</phone>
    <phone_ext>46618</phone_ext>
  </overall_contact>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire de Québec</name>
      <address>
        <city>Québec</city>
        <state>Quebec</state>
        <zip>G1V 2L9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Melissa Laflamme, MD, MSc</last_name>
      <phone>418-525-4444</phone>
      <phone_ext>46618</phone_ext>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>September 15, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2014</study_first_posted>
  <last_update_submitted>July 17, 2018</last_update_submitted>
  <last_update_submitted_qc>July 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>CHU de Quebec-Universite Laval</investigator_affiliation>
    <investigator_full_name>Mélissa Laflamme</investigator_full_name>
    <investigator_title>MD, MSc, FRCSC, Orthopedic surgeon</investigator_title>
  </responsible_party>
  <keyword>Rheumatoid arthritis</keyword>
  <keyword>Surgical Wound Infection</keyword>
  <keyword>Surgical Site Infection</keyword>
  <keyword>Antirheumatic Agents</keyword>
  <keyword>Perioperative Care</keyword>
  <keyword>Anti-TNF</keyword>
  <keyword>Anti-TNF-alpha</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adalimumab</mesh_term>
    <mesh_term>Infliximab</mesh_term>
    <mesh_term>Golimumab</mesh_term>
    <mesh_term>Certolizumab Pegol</mesh_term>
    <mesh_term>Etanercept</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02242474
org study id: 1-levallee
nct id: NCT02242474
lead sponsor: 
has dmc: Yes
Rheumatoid arthritis (RA) is a frequent inflammatory arthritis that can lead to severe joint
      deformity and often requires orthopaedic surgical interventions. Anti-Tumor Necrosis Factor α
      (anti-TNFα) are biological disease-modifying antirheumatic drugs (DMARDs) increasingly used
      in the treatment of rheumatoid arthritis. An increased risk of opportunistic infection was
      demonstrated in patients treated with those drugs. This observation led many national
      committees to recommend anti-TNFα suspension in the perioperative period to avoid a raise in
      the postoperative infection risk in those patients. This approach is not supported by the
      data available in the current literature and it exposes patients to an increased risk of
      inflammatory flare ups of their disease during and after anti-TNFα suspension, which can
      compromise their postoperative rehabilitation and their quality of life.

      The objective of this prospective randomized multicentric trial is to determine the effect of
      anti-TNFα suspension in the perioperative period on the postoperative infection risk.
      Overall, 660 rheumatoid arthritis patients requiring an elective foot or ankle surgery will
      be randomized into two groups. In the first group, anti-TNFα will be stopped 3 half-lives
      before the surgery while they will be continued in the second group. The postoperative
      infection rate will be compared between the two groups. Postoperative complication rates,
      flares and revision surgeries as well as the functional improvement will be compared.

      The study hypothesis is that there is no significant difference in the risk of postoperative
      infection between the two groups.

      Results from this study will help determine the optimal way to use anti-TNFα in the
      perioperative period and will therefore improve the quality of life of rheumatoid arthritis
      patients.
A. STUDY DESIGN This is a prospective randomized multicentric trial. Patients will be
      randomized into two groups. Patients in Group A will continue their anti-TNF treatment during
      the whole perioperative period. Anti-TNFα medication will be suspended prior to the surgery
      in patients randomized in Group B. This design will allow us to minimize the important
      selection bias that was affecting the observational studies previously conducted on this
      topic. Due to safety concerns, patients and evaluators will not be blinded to the treatment.

      B. RESEARCH LOCATION Considering the important number of patients required, we plan on
      conducting a multicentric study. This will allow us to recruit enough patients in a
      reasonable time frame to ensure sufficient power to our results. The main center where the
      data will be gathered is the CHU de Québec. Other centers in Canada will be invited to
      participate in the study for a maximum of 10 centers.

      C. INTERVENTION Medication Patients randomized to Group A will continue their anti-TNFα
      treatment unaltered during the whole perioperative period. Surgery will be performed without
      consideration in regards to the timing of the treatment. The time elapsed between the last
      anti-TNFα administration and the surgery will nonetheless be documented.

      Patients randomized to Group B will have their anti-TNFα therapy interrupted before surgery.
      There is no consensus on the optimal timing of anti-TNFα suspension before surgery. Many
      published guidelines suggest that the pharmacokinetics of the different anti-TNFα medications
      should be an important consideration in the perioperative management of these drugs.
      Different authors suggested that anti-TNFα therapies should be suspended between two and five
      half-lives prior to surgery. Similar timing was used in previous publications. In the current
      trial, anti-TNFα will be suspended three half-lives (± seven days) prior to surgery. All
      other medications used in the treatment of the disease (methotrexate, hydroxychloroquine,
      corticosteroid, etc.) will be documented and continued in the perioperative period.
      Non-steroidal anti-inflammatory drugs (NSAID) will be suspended seven days prior to surgery
      and will be restarted postoperatively. Anti-TNFα will be restarted once wound healing is
      completed.

      Surgery

      All surgeries will be performed by experimented orthopaedic surgeons. Surgical techniques
      will be determined by the treating surgeon and will not be subject to randomization. For
      analysis purposes, surgeries will be subdivided in surgeries with and without permanent
      implants. It will also be divided between forefoot, midfoot, hindfoot and ankle surgeries.
      Use of prophylactic antibiotics will be standardized as follow:

        -  Cephalexin 2g IV before the incision or,

        -  Clindamycin 600mg IV before the incision if patient is allergic to cephalexin D.
           RANDOMIZATION Randomization will be completed as soon as the inclusion and exclusion
           criteria are verified and the patient has given informed consent. Patients will be
           randomized to treatment Group A or B. Randomization will be performed in blocks of 10
           using the web site Randomizer.org. Blocks of 10 numbered, sealed and opaque envelopes
           will be sent to the participating centers.

      E. FOLLOW-UP SCHEDULE Patients will be followed for one year after surgery. There is going to
      be one visit before surgery and five follow-up visits at two weeks, six week, three months,
      six months and 12 months after surgery.

      F. SAMPLE SIZE CALCULATION We calculated the sample size needed to test for equivalence
      between the two groups with a statistical power of 80% and a type I error (alpha) of 5%. The
      observed rate of infection following foot and ankle surgery in RA patient varies greatly in
      the literature [46]. For the purpose of the sample size calculation, we used a 5% rate of
      infection and considered a relative risk of 2 to be clinically significant.

      N1 = N2 = 2*((1.96+0.845)/0.05)^2*0.05*(1-0.05) = 299

      Considering a rate of lost to follow-up of 15%, we concluded that a sample of 660 patients,
      330 in each treatment group, would provide us relevant results.

      G. STATISTICAL ANALYSIS Descriptive analysis Demographic data and baseline clinical
      characteristics obtained will be analyzed. For each continuous variable, the mean, the
      median, the standard deviation as well as the maximum and minimum values are going to be
      presented for each group. For categorical variable, the frequencies and proportions are going
      to be presented. All these variables are going to be compared between the two groups using
      Student's T-test for continuous variables and the Chi-squared test for categorical variables.

      Main analysis The main outcome analysis is going to be made using the Chi-squared test. The
      gross surgical site infection (SSI) relative risk between the two groups will be calculated.
      The relative risk will also be adjusted using a multivariate regression analysis that will
      consider relevant demographic variables. The model will include, but will not be limited, to
      the variables that are statistically different between the two groups. Secondary outcomes
      related to disease flare up, poor wound healing and reoperation rate will also be analyzed
      using Chi-squared test. A linear regression model with repeated measures will be used to
      compare functional scores improvements between the two groups.

      Sub-group analysis will be performed. They will include analysis by type of surgery, by use
      of permanent implants, by baseline disease activity level and by type of anti-TNFα used.

      Interim analysis An interim analysis will be performed at the midpoint of the recruitment
      period to look for a significant difference in the primary outcome between the two groups.
      The analysis will take place when 330 patients will have been followed for at least six weeks
      after surgery. Based on the obtained results, a decision to interrupt the trial could
      eventually be made by the safety committee.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Surgical site infection
time frame: Within one year after surgery
description: Surgical site infection will be determined according to the definition of the Center for Disease Control (CDC).
measure: Disease flare up
time frame: From the time the drug is suspended until one year after surgery
description: There is currently no widely accepted definition of RA disease flare up. In this study, patients satisfying one of the two following criteria will be considered as having a disease flare up:
I. Modification of the medication made necessary by an increase in the disease symptoms.
II. Increase in disease activity according to the Clinical Disease Activity Index (CDAI):
Increase from a remission or a low disease activity level at baseline to a moderate or high activity level.
or
Increase from a moderate disease activity level at baseline to a high activity level.
or
An increase of 12 points or more on the CDAI in patients having a high disease activity level at baseline.
measure: Change in functional level
time frame: Until one year after surgery
description: The functional level of each patient is going to be assessed using the Health Assessment Questionnaire (HAQ) before and after the surgery in accordance with the follow-up schedule presented in the protocol.
measure: Poor wound healing
time frame: Within one year of surgery or until wound is completely healed
description: Complications associated with poor wound healing such as delayed wound healing and dehiscence will be noted. Delayed wound healing will be defined as a wound that isn't completely healed 14 days after surgery. Dehiscence will be defined as a wound that requires secondary closure or a wound that heals by secondary intention.
measure: Reoperation rate
time frame: Within one year of surgery
description: All reoperations made necessary following postoperative complications (ex : infection, implant retrieval, debridement) will be documented. More than one reoperation can be performed for the same patient. The reoperation rate expressed as a percentage will be compared between the two groups.
measure: Other adverse events
time frame: Within one year of surgery
description: All other significant adverse events will be documented. For example, systemic infection, septic choc, implant loosening and arthrodesis nonunion are going to be noted. Nonunion is going to be defined as the persistence of a joint space on more than 50% of the articular surface visible on CT-Scan six months after surgery associated with pain.
arm group label: Anti-TNF suspended perioperatively
arm group type: Active Comparator
description: Patients randomized to Group B will have their anti-TNFα therapy interrupted before surgery. Different authors suggested that anti-TNFα therapies should be suspended between two and five half-lives prior to surgery. In the current trial, anti-TNFα will be suspended three half-lives (± seven days) prior to surgery. All other medications used in the treatment of the disease (methotrexate, hydroxychloroquine, corticosteroid, etc.) will be documented and continued in the perioperative period. Non-steroidal anti-inflammatory drugs (NSAID) will be suspended seven days prior to surgery and will be restarted postoperatively. Anti-TNFα will be restarted once wound healing is completed.
arm group label: Anti-TNFα continued perioperatively
arm group type: Experimental
description: Patients randomized to Group A will continue their anti-TNFα treatment unaltered during the whole perioperative period. Surgery will be performed without consideration in regards to the timing of the treatment. The time elapsed between the last anti-TNFα administration and the surgery will nonetheless be documented.
intervention type: Drug
intervention name: Anti-TNF suspended perioperatively
arm group label: Anti-TNF suspended perioperatively
other name: Infliximab
other name: Remicade
other name: Etanercept
other name: Enbrel
other name: Adalimumab
other name: Humira
other name: Certolizumab
other name: Cimzia
other name: Golimumab
other name: Simponi
intervention type: Drug
intervention name: Anti-TNFα continued perioperatively
arm group label: Anti-TNFα continued perioperatively
other name: Infliximab
other name: Remicade
other name: Etanercept
other name: Enbrel
other name: Adalimumab
other name: Humira
other name: Certolizumab
other name: Cimzia
other name: Golimumab
other name: Simponi
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mélissa Laflamme, MD, MsC
role: Principal Investigator
affiliation: Centre Hôspitalier Universitaire de Québec
last name: Melissa Laflamme, MD, MSc
phone: 418-525-4444
phone ext: 46618
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: CHU de Quebec-Universite Laval
investigator full name: Mélissa Laflamme
investigator title: MD, MSc, FRCSC, Orthopedic surgeon
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Adalimumab
mesh term: Infliximab
mesh term: Golimumab
mesh term: Certolizumab Pegol
mesh term: Etanercept
mesh term: Antibodies, Monoclonal