<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/NCT03830931</url>
  </required_header>
  <id_info>
    <org_study_id>SKAR1</org_study_id>
    <nct_id>NCT03830931</nct_id>
  </id_info>
  <brief_title>Postoperative Hyperglycemia After Knee Primary Knee Arthroplasty Surgery</brief_title>
  <official_title>Hyperglycemia in Knee Arthroplasty Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lund University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Health and Social Affairs, Sweden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Lund University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients in three hospitals in Sweden who will have knee arthroplasty surgery for the first&#xD;
      time are invited to participate in the study, approximately 2000 patients. The fasting&#xD;
      glucose value (fP-glucose) is obtained via a blood sample the day after the knee arthroplasty&#xD;
      surgery. The sample is analyzed and the glucose value obtained is documented and sent to the&#xD;
      Swedish Knee Arthroplasty Register (SKAR). In the SKAR there is information on patient&#xD;
      characteristics, diagnosis, prosthesis, anesthetic form and primary and secondary operations,&#xD;
      etc. The unique personal numbers of the included patients are submitted to the National Board&#xD;
      of Health and Welfare, which matches the cohort with the Patient Register to identify adverse&#xD;
      events, re-admission and death in a year after the surgery. SKAR has carried out several&#xD;
      interactions with the National Board of Health and Welfare, and possesses clinical expertise&#xD;
      as well as registers and biostatistics expertise. Incidence calculation of the proportion&#xD;
      that develops elevated glucose levels after surgery and Cox regression for group comparison&#xD;
      (elevated glucose vs. non-elevated) taking into account factors within groups such as age,&#xD;
      gender, etc. This is a register-based observation study. Since the incidence of elevated&#xD;
      glucose value after a knee prosthesis operation is not known, we are planning for a&#xD;
      representative selection from three major prosthetic clinics in Sweden. Regarding the&#xD;
      secondary purposes, our ability to answer these depends on the presence of elevated glucose&#xD;
      levels. The inclusion start in January 2019 and lasts for one year. Incidence calculations&#xD;
      can be made as soon as all patients are included, but 90-day data from the patient register&#xD;
      can reasonably be completed&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Purpose&#xD;
&#xD;
      To reduce the risk of prosthetic joint infection (PJI) after primary knee arthroplasty&#xD;
      surgery.&#xD;
&#xD;
      The aims are to study:&#xD;
&#xD;
        -  the presence of postoperative hyperglycemia after knee arthroplasty.&#xD;
&#xD;
        -  if there is an increased risk of wound disturbance&#xD;
&#xD;
        -  if there is an increased risk of PJI.&#xD;
&#xD;
        -  if there is an increased risk of other complications, re-admissions and mortality.&#xD;
&#xD;
        -  if postoperative hyperglycemia is more common after general than spinal anesthesia.&#xD;
&#xD;
        -  if patients developing hyperglycemia has longer hospital stay.&#xD;
&#xD;
      Background&#xD;
&#xD;
      Postoperative hyperglycemia is a consequence of the insulin resistance that may occur in&#xD;
      otherwise healthy nondiabetic patients after uncomplicated elective surgery (Thorell et al.&#xD;
      1999). Hyperglycemia has been associated with an increased risk of PJI (Mraovic et al. 2011)&#xD;
      and to be a risk factor in many common postoperative complications (van den Berghe et al.&#xD;
      2001).&#xD;
&#xD;
      Knee arthroplasty surgery in Sweden has more than doubled since the millennium with more than&#xD;
      14,000 primary knee arthroplasties in 2016. The risk of revision after a primary knee&#xD;
      arthroplasty is the lowest reported in the world (less than 5% after 10 years in total knee&#xD;
      arthroplasty) (SKAR 2017). However during the latest 10 years the risk of revision due to&#xD;
      infection has increased as compared to the previous 10 years. PJI is an uncommon&#xD;
      complication, 1% - 1.5% (SKAR 2017), but devastating for the patient and an expensive&#xD;
      complication for the health care and the society.&#xD;
&#xD;
      During 2009-2013 the Prosthetic Related Infections Shall be Stopped project (PRISS) was&#xD;
      performed in Sweden. The purpose of that project was to half the risk of PJI in knee and hip&#xD;
      arthroplasties by optimizing the routines. All hospitals performing knee and hip arthroplasty&#xD;
      surgery in Sweden participated (www.lof.se). The PRISS project resulted in, among other&#xD;
      things, documents/recommendations including a compilation and evaluation of the best-known&#xD;
      knowledge within four important areas; risk factor and optimizing, prophylactic antibiotics,&#xD;
      follow-up and infection registration and optimal operation room environment. These documents&#xD;
      are updated every second year or in case of new knowledge. One of the issues that the expert&#xD;
      group, within risk factors and optimizing, requested was further research concerning if&#xD;
      screening for hyperglycemia in patients with unknown diabetes has an effect on the risk of&#xD;
      PJI (www.lof.se).&#xD;
&#xD;
      Postoperative hyperglycemia has been shown to be relatively common (Pili-Floury et al. 2009,&#xD;
      Jämsen et al. 2015). Pili-Floury et al. (2009) showed that 29/38 patients without a medical&#xD;
      history of diabetes before the surgery became hyperglycemic for the first two days following&#xD;
      arthroplasty surgery. A study from a Finnish hospital found that one fourth (47/191) of the&#xD;
      hip and knee arthroplasty patients included in the study had pre-diabetes (increased fasting&#xD;
      glucose and/or impaired glucose tolerance) and half of these patients (24/47) developed&#xD;
      perioperative hyperglycemia (Jämsen et al. 2015).&#xD;
&#xD;
      Prevention and treatment of insulin resistance has been shown to have an effect on morbidity,&#xD;
      mortality, and recovery after surgery (Ljungqvist et al. 2007). It has been suggested that&#xD;
      insulin resistance can be avoided using epidural analgesia, minimally invasive surgical&#xD;
      technique, optimal pain control, and preoperative carbohydrate treatment (Ljungqvist et al.&#xD;
      2007). General anesthesia has become more common in Sweden and was used in 30% of the surgery&#xD;
      during 2016 with large variations between hospitals. Minimal invasive surgery is sometimes&#xD;
      used in uni-compartmental knee arthroplasty (UKA) but not in total knee arthroplasty (TKA) in&#xD;
      Sweden (SKAR 2017). The hospitals use standardized multi-modal pain control including local&#xD;
      infiltration analgesia (LIA), while the use of preoperative carbohydrate treatment may vary.&#xD;
&#xD;
      There are no general recommendations in Sweden to measure fasting glucose levels and/or HBA1c&#xD;
      either preoperatively or postoperatively in knee arthroplasty patients unless they have&#xD;
      diagnosed diabetes. In a survey from the Swedish Knee Arthroplasty Register (SKAR) to all 74&#xD;
      hospitals in Sweden performing knee arthroplasty surgery 2017, only 5 hospitals routinely&#xD;
      obtained fasting plasma glucose (fP-Glucose). In these hospitals, patients having an elevated&#xD;
      glucose level are submitted to the primary care for further investigation. The number of such&#xD;
      patients is unknown.&#xD;
&#xD;
      Work plan&#xD;
&#xD;
        1. Study population All patients operated with a primary knee arthroplasty from 1st of&#xD;
           January 2019 to 31st of December 2020 in high volume hospitals will be invited to&#xD;
           participate in the study, approximately 2,000 patients. The operation will be registered&#xD;
           in the SKAR to which all hospitals performing knee arthroplasty surgery in Sweden report&#xD;
           their knee arthroplasties (primaries, revisions and re-operations). The validity of the&#xD;
           register has been considered to be high (coverage 100%, completeness 97%, and response&#xD;
           rate 99%) (SKAR 2017). All variables registered are shown and described in the variable&#xD;
           list (attachment 1).&#xD;
&#xD;
        2. Plasma glucose The pre-, per- and postoperative routines at each hospital will be as&#xD;
           usual, except that for a fP-glucose measurement. In the morning the day after surgery,&#xD;
           fP-Glucose will be measured, using the ordinary routine for blood samples at each&#xD;
           hospital. The glucose level in plasma is reported as millimoles per liter (mmol/L).&#xD;
           According to the Nordic Reference Interval Project (NORIP) the reference interval for&#xD;
           venous and capillary fP-Glucose is 4.2-6.3 mmol/L, i.e. slightly different from the&#xD;
           World Health Organization (WHO) reference value which is &lt;6.1 mmol/L.&#xD;
&#xD;
           The result of the test will be documented on a form (attachment 2) that includes the&#xD;
           patient's personal identification (ID), the date of fP-Glucose measurement, if the&#xD;
           patient has diabetes (type 1 or 2) or not and in case of diabetes what treatment (diet,&#xD;
           tablets, insulin). The form will be sent to the SKAR and entered in a separate file&#xD;
           which can be linked to the SKAR database. Using the SKAR will provide information on the&#xD;
           proportion of patients participating in the study as well as for their follow-up with&#xD;
           respect to further surgeries or complications.&#xD;
&#xD;
        3. Prosthetic joint infection Revisions and re-operations due to infection or suspected&#xD;
           infection as well as other causes after primary knee arthroplasty are registered in the&#xD;
           SKAR (attachment 1). Patients treated for infection or suspected infections not&#xD;
           requiring surgery are documented in the department's local infection register at each&#xD;
           hospital respectively.&#xD;
&#xD;
        4. Other complications, re-admissions and mortality The SKAR has together with the National&#xD;
           Board of Health and Welfare examined the ICD10 and the Nordic Medico-Statistical&#xD;
           Committee codes (NOMESCO, a classification of surgical procedures) that occur in the&#xD;
           National Patient Register (NPR) during admission for, and after knee arthroplasty. This&#xD;
           has resulted in a longer list of codes that may represent adverse events when they occur&#xD;
           during the hospital stay or in readmissions within 90 days and 1 year of surgery (SKAR).&#xD;
           The SKAR will send data on registered patients to the NPR which performs the match. The&#xD;
           NPR will check if they during the hospital stay or within 1 year of the surgery received&#xD;
           ICD10 and/or procedure codes that correspond to the definition of adverse events.&#xD;
&#xD;
        5. Length of hospital stay The length of hospital stay for each patient is obtained from&#xD;
           the electronic record system used by the orthopedic departments at each site.&#xD;
&#xD;
        6. Statistics The primary aim of this register-based, observational, study is to&#xD;
           investigate how common postoperative hyperglycemia is after knee arthroplasty. The&#xD;
           secondary aim is to investigate if hyperglycemic patients have an increased risk of PJI&#xD;
           or adverse events and if hyperglycemia is more common after general than spinal&#xD;
           anesthesia.&#xD;
&#xD;
           The proportion of hyperglycemia patients in Sweden is unknown. The study is to be&#xD;
           performed at large arthroplasty units that operate approximately 400-800 knee&#xD;
           arthroplasties/year. Assuming that the proportion of patients with hyperglycemia is&#xD;
           similar to that in the Finnish study, i.e. 25% (Jämsen et al. 2015), the hospitals&#xD;
           together operate 1800 primary knee arthroplasties during one year and that 80% of the&#xD;
           patients accept to participate in the study, would result in 450 patients having&#xD;
           hyperglycemia. This would provide a reasonable material for evaluation of risks&#xD;
           concerning infections and adverse events.&#xD;
&#xD;
        7. Ethics In some hospitals in Sweden, fP-glucose is a routine while in those hospitals&#xD;
           included in the planed study it is not. However in the morning the day after surgery the&#xD;
           hemoglobin value is controlled routinely and performed at the included hospitals. From&#xD;
           the same splinter as hemoglobin is taken in the finger or vein, fP-glucose can be&#xD;
           obtained. The splinter in the finger or vein may be painful and experienced as&#xD;
           unpleasant by the patients instantly but this additional test will not cause any further&#xD;
           discomfort. The patients will be sent written information (attachment 2) about the study&#xD;
           together with the invitation for the preoperative visit at each hospital. At the&#xD;
           preoperative visit the patients has possibility to further questions if requested.&#xD;
           Considering the patients integrity all results will be presented on aggregated level and&#xD;
           the material is relatively large and the risk for individual identification may be seen&#xD;
           as negligible.&#xD;
&#xD;
      Importance&#xD;
&#xD;
      Currently, we have no knowledge on the prevalence of postoperative hyperglycemia after knee&#xD;
      arthroplasty in patients without diagnosed diabetes or its effect on outcome. Prosthetic&#xD;
      joint infection is a devastating complication for the patients as well as it is costly for&#xD;
      the health care and the society. Should postoperative hyperglycemia be a risk factor in the&#xD;
      development of PJI it may be a modifiable risk factor by prevention and/or treatment.&#xD;
&#xD;
      By including patients having a primary knee arthroplasty we will gain knowledge on the&#xD;
      proportion of patients without diagnosed diabetes having elevated postoperative glucose&#xD;
      values and to evaluate if such patients run an increased risk of PJI or other adverse events.&#xD;
&#xD;
      Further, general anesthesia during arthroplasty surgery has become more popular in Sweden in&#xD;
      recent years. However, it has been suggested that general anesthesia may be increase the risk&#xD;
      for hyperglycemia after surgery (Ljungqvist et al. 2007). Thus, this study may help us find&#xD;
      out if this is the case or not.&#xD;
&#xD;
      Dependent on the findings of the study, a continuation may be needed in order to evaluate the&#xD;
      possible benefit of a general preoperative screening in arthroplasty patients.&#xD;
&#xD;
      Additional/Safety&#xD;
&#xD;
      Patients with elevated postoperative fP-Glucose level will be followed-up by the primary&#xD;
      care. In case of fP-Glucose levels associated with diabetes the routines of the department&#xD;
      will be followed.&#xD;
&#xD;
      Time-frame The collection of data will start January 1st 2019 if all permissions are granted&#xD;
      and continue until December 31st 19. During 2019-2020 the patients will be followed in the&#xD;
      SKAR as well in medical journals and local infection registers. When the last patient is&#xD;
      included we may have the possibility to present the frequency of hyperglycemia after knee&#xD;
      arthroplasty surgery in the hospitals included. The data from the NPR for patients&#xD;
      participating in the study will probably not be ready until the spring 2020. In the summer&#xD;
      2020 we may have data from the Patient register for complications, readmission and death&#xD;
      during the first 90 day after surgery and be able to present a short follow-up. During the&#xD;
      spring 2021 we may have the 1 year follow-up from the NPR.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Actual">October 31, 2021</completion_date>
  <primary_completion_date type="Actual">September 28, 2021</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>1 Year</target_duration>
  <primary_outcome>
    <measure>The presence of postoperative hyperglycemia after primary knee arthroplasty surgery</measure>
    <time_frame>The postoperative fP-Glucose will be assessed 1 day after primary knee arthroplasty surgery</time_frame>
    <description>fP-Glucose</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The presence of adverse events after primary knee arthroplasty surgery</measure>
    <time_frame>90-days after primary knee arthroplasty surgery</time_frame>
    <description>complications, readmission, death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The presence of prosthetic joint infection (PJI) after primary knee arhroplasty surgery</measure>
    <time_frame>within 1 year after primary knee arthroplasty surgery</time_frame>
    <description>infection after primary knee arthroplasty surgery</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">1448</enrollment>
  <condition>Hyperglycemia</condition>
  <arm_group>
    <arm_group_label>Primary knee arthroplasty patients</arm_group_label>
    <description>Fasting Plasma Glucose test will be obtained the morning after surgery and the frequency of hyperglycemia in non diabetic and diabetic patients will be evaluated</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood sample&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients operated on with a primary knee arthroplasty from Three hospitals in Sweden&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients operated on with a primary knee arthroplasty in 3 hospitals in Sweden.&#xD;
&#xD;
          -  Approved to participate in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not approved to participate in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Annette W-Dahl, Ass prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Swedish Knee Arthroplasty Register</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Swedish Knee Arthroplasty Register</name>
      <address>
        <city>Lund</city>
        <state>Skane</state>
        <zip>24651</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>February 4, 2019</study_first_submitted>
  <study_first_submitted_qc>February 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 5, 2019</study_first_posted>
  <last_update_submitted>November 10, 2021</last_update_submitted>
  <last_update_submitted_qc>November 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hyperglycemia, arthroplasty , complication</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperglycemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03830931
org study id: SKAR1
nct id: NCT03830931
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patients in three hospitals in Sweden who will have knee arthroplasty surgery for the first
      time are invited to participate in the study, approximately 2000 patients. The fasting
      glucose value (fP-glucose) is obtained via a blood sample the day after the knee arthroplasty
      surgery. The sample is analyzed and the glucose value obtained is documented and sent to the
      Swedish Knee Arthroplasty Register (SKAR). In the SKAR there is information on patient
      characteristics, diagnosis, prosthesis, anesthetic form and primary and secondary operations,
      etc. The unique personal numbers of the included patients are submitted to the National Board
      of Health and Welfare, which matches the cohort with the Patient Register to identify adverse
      events, re-admission and death in a year after the surgery. SKAR has carried out several
      interactions with the National Board of Health and Welfare, and possesses clinical expertise
      as well as registers and biostatistics expertise. Incidence calculation of the proportion
      that develops elevated glucose levels after surgery and Cox regression for group comparison
      (elevated glucose vs. non-elevated) taking into account factors within groups such as age,
      gender, etc. This is a register-based observation study. Since the incidence of elevated
      glucose value after a knee prosthesis operation is not known, we are planning for a
      representative selection from three major prosthetic clinics in Sweden. Regarding the
      secondary purposes, our ability to answer these depends on the presence of elevated glucose
      levels. The inclusion start in January 2019 and lasts for one year. Incidence calculations
      can be made as soon as all patients are included, but 90-day data from the patient register
      can reasonably be completed
Purpose

      To reduce the risk of prosthetic joint infection (PJI) after primary knee arthroplasty
      surgery.

      The aims are to study:

        -  the presence of postoperative hyperglycemia after knee arthroplasty.

        -  if there is an increased risk of wound disturbance

        -  if there is an increased risk of PJI.

        -  if there is an increased risk of other complications, re-admissions and mortality.

        -  if postoperative hyperglycemia is more common after general than spinal anesthesia.

        -  if patients developing hyperglycemia has longer hospital stay.

      Background

      Postoperative hyperglycemia is a consequence of the insulin resistance that may occur in
      otherwise healthy nondiabetic patients after uncomplicated elective surgery (Thorell et al.
      1999). Hyperglycemia has been associated with an increased risk of PJI (Mraovic et al. 2011)
      and to be a risk factor in many common postoperative complications (van den Berghe et al.
      2001).

      Knee arthroplasty surgery in Sweden has more than doubled since the millennium with more than
      14,000 primary knee arthroplasties in 2016. The risk of revision after a primary knee
      arthroplasty is the lowest reported in the world (less than 5% after 10 years in total knee
      arthroplasty) (SKAR 2017). However during the latest 10 years the risk of revision due to
      infection has increased as compared to the previous 10 years. PJI is an uncommon
      complication, 1% - 1.5% (SKAR 2017), but devastating for the patient and an expensive
      complication for the health care and the society.

      During 2009-2013 the Prosthetic Related Infections Shall be Stopped project (PRISS) was
      performed in Sweden. The purpose of that project was to half the risk of PJI in knee and hip
      arthroplasties by optimizing the routines. All hospitals performing knee and hip arthroplasty
      surgery in Sweden participated (www.lof.se). The PRISS project resulted in, among other
      things, documents/recommendations including a compilation and evaluation of the best-known
      knowledge within four important areas; risk factor and optimizing, prophylactic antibiotics,
      follow-up and infection registration and optimal operation room environment. These documents
      are updated every second year or in case of new knowledge. One of the issues that the expert
      group, within risk factors and optimizing, requested was further research concerning if
      screening for hyperglycemia in patients with unknown diabetes has an effect on the risk of
      PJI (www.lof.se).

      Postoperative hyperglycemia has been shown to be relatively common (Pili-Floury et al. 2009,
      Jämsen et al. 2015). Pili-Floury et al. (2009) showed that 29/38 patients without a medical
      history of diabetes before the surgery became hyperglycemic for the first two days following
      arthroplasty surgery. A study from a Finnish hospital found that one fourth (47/191) of the
      hip and knee arthroplasty patients included in the study had pre-diabetes (increased fasting
      glucose and/or impaired glucose tolerance) and half of these patients (24/47) developed
      perioperative hyperglycemia (Jämsen et al. 2015).

      Prevention and treatment of insulin resistance has been shown to have an effect on morbidity,
      mortality, and recovery after surgery (Ljungqvist et al. 2007). It has been suggested that
      insulin resistance can be avoided using epidural analgesia, minimally invasive surgical
      technique, optimal pain control, and preoperative carbohydrate treatment (Ljungqvist et al.
      2007). General anesthesia has become more common in Sweden and was used in 30% of the surgery
      during 2016 with large variations between hospitals. Minimal invasive surgery is sometimes
      used in uni-compartmental knee arthroplasty (UKA) but not in total knee arthroplasty (TKA) in
      Sweden (SKAR 2017). The hospitals use standardized multi-modal pain control including local
      infiltration analgesia (LIA), while the use of preoperative carbohydrate treatment may vary.

      There are no general recommendations in Sweden to measure fasting glucose levels and/or HBA1c
      either preoperatively or postoperatively in knee arthroplasty patients unless they have
      diagnosed diabetes. In a survey from the Swedish Knee Arthroplasty Register (SKAR) to all 74
      hospitals in Sweden performing knee arthroplasty surgery 2017, only 5 hospitals routinely
      obtained fasting plasma glucose (fP-Glucose). In these hospitals, patients having an elevated
      glucose level are submitted to the primary care for further investigation. The number of such
      patients is unknown.

      Work plan

        1. Study population All patients operated with a primary knee arthroplasty from 1st of
           January 2019 to 31st of December 2020 in high volume hospitals will be invited to
           participate in the study, approximately 2,000 patients. The operation will be registered
           in the SKAR to which all hospitals performing knee arthroplasty surgery in Sweden report
           their knee arthroplasties (primaries, revisions and re-operations). The validity of the
           register has been considered to be high (coverage 100%, completeness 97%, and response
           rate 99%) (SKAR 2017). All variables registered are shown and described in the variable
           list (attachment 1).

        2. Plasma glucose The pre-, per- and postoperative routines at each hospital will be as
           usual, except that for a fP-glucose measurement. In the morning the day after surgery,
           fP-Glucose will be measured, using the ordinary routine for blood samples at each
           hospital. The glucose level in plasma is reported as millimoles per liter (mmol/L).
           According to the Nordic Reference Interval Project (NORIP) the reference interval for
           venous and capillary fP-Glucose is 4.2-6.3 mmol/L, i.e. slightly different from the
           World Health Organization (WHO) reference value which is <6.1 mmol/L.

           The result of the test will be documented on a form (attachment 2) that includes the
           patient's personal identification (ID), the date of fP-Glucose measurement, if the
           patient has diabetes (type 1 or 2) or not and in case of diabetes what treatment (diet,
           tablets, insulin). The form will be sent to the SKAR and entered in a separate file
           which can be linked to the SKAR database. Using the SKAR will provide information on the
           proportion of patients participating in the study as well as for their follow-up with
           respect to further surgeries or complications.

        3. Prosthetic joint infection Revisions and re-operations due to infection or suspected
           infection as well as other causes after primary knee arthroplasty are registered in the
           SKAR (attachment 1). Patients treated for infection or suspected infections not
           requiring surgery are documented in the department's local infection register at each
           hospital respectively.

        4. Other complications, re-admissions and mortality The SKAR has together with the National
           Board of Health and Welfare examined the ICD10 and the Nordic Medico-Statistical
           Committee codes (NOMESCO, a classification of surgical procedures) that occur in the
           National Patient Register (NPR) during admission for, and after knee arthroplasty. This
           has resulted in a longer list of codes that may represent adverse events when they occur
           during the hospital stay or in readmissions within 90 days and 1 year of surgery (SKAR).
           The SKAR will send data on registered patients to the NPR which performs the match. The
           NPR will check if they during the hospital stay or within 1 year of the surgery received
           ICD10 and/or procedure codes that correspond to the definition of adverse events.

        5. Length of hospital stay The length of hospital stay for each patient is obtained from
           the electronic record system used by the orthopedic departments at each site.

        6. Statistics The primary aim of this register-based, observational, study is to
           investigate how common postoperative hyperglycemia is after knee arthroplasty. The
           secondary aim is to investigate if hyperglycemic patients have an increased risk of PJI
           or adverse events and if hyperglycemia is more common after general than spinal
           anesthesia.

           The proportion of hyperglycemia patients in Sweden is unknown. The study is to be
           performed at large arthroplasty units that operate approximately 400-800 knee
           arthroplasties/year. Assuming that the proportion of patients with hyperglycemia is
           similar to that in the Finnish study, i.e. 25% (Jämsen et al. 2015), the hospitals
           together operate 1800 primary knee arthroplasties during one year and that 80% of the
           patients accept to participate in the study, would result in 450 patients having
           hyperglycemia. This would provide a reasonable material for evaluation of risks
           concerning infections and adverse events.

        7. Ethics In some hospitals in Sweden, fP-glucose is a routine while in those hospitals
           included in the planed study it is not. However in the morning the day after surgery the
           hemoglobin value is controlled routinely and performed at the included hospitals. From
           the same splinter as hemoglobin is taken in the finger or vein, fP-glucose can be
           obtained. The splinter in the finger or vein may be painful and experienced as
           unpleasant by the patients instantly but this additional test will not cause any further
           discomfort. The patients will be sent written information (attachment 2) about the study
           together with the invitation for the preoperative visit at each hospital. At the
           preoperative visit the patients has possibility to further questions if requested.
           Considering the patients integrity all results will be presented on aggregated level and
           the material is relatively large and the risk for individual identification may be seen
           as negligible.

      Importance

      Currently, we have no knowledge on the prevalence of postoperative hyperglycemia after knee
      arthroplasty in patients without diagnosed diabetes or its effect on outcome. Prosthetic
      joint infection is a devastating complication for the patients as well as it is costly for
      the health care and the society. Should postoperative hyperglycemia be a risk factor in the
      development of PJI it may be a modifiable risk factor by prevention and/or treatment.

      By including patients having a primary knee arthroplasty we will gain knowledge on the
      proportion of patients without diagnosed diabetes having elevated postoperative glucose
      values and to evaluate if such patients run an increased risk of PJI or other adverse events.

      Further, general anesthesia during arthroplasty surgery has become more popular in Sweden in
      recent years. However, it has been suggested that general anesthesia may be increase the risk
      for hyperglycemia after surgery (Ljungqvist et al. 2007). Thus, this study may help us find
      out if this is the case or not.

      Dependent on the findings of the study, a continuation may be needed in order to evaluate the
      possible benefit of a general preoperative screening in arthroplasty patients.

      Additional/Safety

      Patients with elevated postoperative fP-Glucose level will be followed-up by the primary
      care. In case of fP-Glucose levels associated with diabetes the routines of the department
      will be followed.

      Time-frame The collection of data will start January 1st 2019 if all permissions are granted
      and continue until December 31st 19. During 2019-2020 the patients will be followed in the
      SKAR as well in medical journals and local infection registers. When the last patient is
      included we may have the possibility to present the frequency of hyperglycemia after knee
      arthroplasty surgery in the hospitals included. The data from the NPR for patients
      participating in the study will probably not be ready until the spring 2020. In the summer
      2020 we may have data from the Patient register for complications, readmission and death
      during the first 90 day after surgery and be able to present a short follow-up. During the
      spring 2021 we may have the 1 year follow-up from the NPR.
observational model: Cohort
time perspective: Prospective
measure: The presence of postoperative hyperglycemia after primary knee arthroplasty surgery
time frame: The postoperative fP-Glucose will be assessed 1 day after primary knee arthroplasty surgery
description: fP-Glucose
measure: The presence of adverse events after primary knee arthroplasty surgery
time frame: 90-days after primary knee arthroplasty surgery
description: complications, readmission, death
measure: The presence of prosthetic joint infection (PJI) after primary knee arhroplasty surgery
time frame: within 1 year after primary knee arthroplasty surgery
description: infection after primary knee arthroplasty surgery
arm group label: Primary knee arthroplasty patients
description: Fasting Plasma Glucose test will be obtained the morning after surgery and the frequency of hyperglycemia in non diabetic and diabetic patients will be evaluated
Blood sample
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Annette W-Dahl, Ass prof
role: Principal Investigator
affiliation: The Swedish Knee Arthroplasty Register
facility: 
country: Sweden
responsible party type: Sponsor
mesh term: Hyperglycemia
sharing ipd: No