<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/NCT04448652</url>
  </required_header>
  <id_info>
    <org_study_id>nsaid_syt</org_study_id>
    <secondary_id>18-000315/115</secondary_id>
    <nct_id>NCT04448652</nct_id>
  </id_info>
  <brief_title>Does Omission of NSAIDs After Colorectal Cancer Operation Affect the Consumption of Opioids?</brief_title>
  <official_title>Effects on Omission of NSAIDs on the Consumption of Opioids in the Standard Analgesic Regimen After Elective Laparoscopic Colorectal Cancer Resection in an ERAS Setting. A Retrospective Single-center Cohort Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zealand University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zealand University Hospital</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 undergoing an operation for colorectal cancer are normally treated with&#xD;
      non-steroid-anti-inflammatory-drugs (NSAIDs) e.g. ibuprofen as pain medication after the&#xD;
      operation. It is well known that NSAIDs can be harmful to kidney-and heart patients and some&#xD;
      studies also have shown an increased risc of surgical complications after treatment with&#xD;
      NSAIDs. On the other hand recent studies have found a preventive effect of NSAIDs on&#xD;
      colorectal cancer recurrence thus leaving the colorectal surgeon in doubt whether NSAIDs are&#xD;
      beneficial or harmful to colorectal cancer patients.&#xD;
&#xD;
      In the department of colorectal cancer surgery at Zealand University Hospital it was decided&#xD;
      to leave out NSAIDs from the 1st of april 2016. This study will investigate if there is a&#xD;
      change in consumption of opioids before and after omission of NSAIDs. This will be an&#xD;
      important finding because opioids also have harmful side-effects as well as a risk of&#xD;
      addiction. The investigators will also compare the blood samples and see if there is signs of&#xD;
      impaired renal and cardiac function in the group that was treated with NSAIDs. Finally the&#xD;
      long term outcomes will be investigated such as cancer recurrence and death in the two&#xD;
      groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Many standard analgesic regimens after colorectal cancer surgery includes a NSAID in&#xD;
      combination with paracetamol and other non-opioid analgesics. Concerns about a risk of&#xD;
      cardiovascular and renal impairment and the possible association with anastomotic leaks have&#xD;
      questioned the rationale of NSAID use in the postoperative period and the need for possible&#xD;
      alternatives. In the department of colorectal cancer -surgery of Zealand University Hospital&#xD;
      it was decided to remove NSAIDs from the standard analgesic package from 1th of April 2016&#xD;
      without other analgesic substitution. This change might imply deterioration of the enhanced&#xD;
      recovery program with an increase in the use of opioids and side effects that might cause a&#xD;
      longer length of stay. In addition, recent studies are relaunching ibuprofen as a&#xD;
      chemo-preventive of colorectal cancer thus leaving the colorectal surgeon in doubt whether&#xD;
      NSAIDs are beneficial or harmful to colorectal cancer patients.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      The aim of the present study is to investigate the short- and long-term outcomes before (+&#xD;
      ibuprofen) and after (- ibuprofen) April 1 st 2016.&#xD;
&#xD;
      Methods Design A prospective, consecutive single-center cohort-study. Study population&#xD;
      Patients undergoing elective laparoscopic colorectal cancer resection at Zealand University&#xD;
      Hospital, before and after 1st. of April 2016 are eligible for the study. Patients with a&#xD;
      preoperative use of opioids within the last 3 months, undergoing a palliative resection or&#xD;
      had a surgical complication leading to reoperation in general anesthesia will be excluded.&#xD;
      Palliative resection is defined as patients with symptomatic metastatic colorectal cancer&#xD;
      that undergoes resection of the primary tumor with the aim to relieve symptoms such as&#xD;
      obstruction, bleeding or perforation.&#xD;
&#xD;
      Before April 1st. 2016 all patients, regardless of cardiovascular morbidity or kidney&#xD;
      disease, received ibuprofen 400 mg in combination with paracetamol 1000 mg four times a day&#xD;
      in the postoperative period and until admission. After April 1st the patients only received&#xD;
      paracetamol. If the standard analgesic regimen was insufficient, patients in both groups were&#xD;
      treated with intravenous, subcutaneous or oral opioids defined as drugs within the ACT-code&#xD;
      (Anatomical Therapeutic Chemical Classification System) N02A. The department has a&#xD;
      well-implemented Enhanced Recovery After Surgery (ERAS) program with a standardized&#xD;
      management of the perioperative course and discharge with no other changes in the program in&#xD;
      the study period.&#xD;
&#xD;
      Demographic and perioperative data including length of stay and postoperative complications&#xD;
      within 30 days will be collected from the national prospective database of the Danish&#xD;
      Colorectal Cancer Group. According to the exclusion criteria all patients with a registered&#xD;
      surgical complication clavien dindo ≥3b will be excluded. The postoperative medical&#xD;
      complications are categorized in the database in: Stroke, acute myocardial infarction,&#xD;
      aspiration, pneumonia, heart failure, lung embolism, respiratory insufficiency, kidney&#xD;
      failure, sepsis, deep venous thrombosis, arterial embolism and &quot;other medical complication&quot;.&#xD;
      The medical complications are also graded according to the clavien-dindo classification&#xD;
      system. Daily postoperative opioid consumption until discharge, readmissions within 30 days,&#xD;
      colorectal cancer recurrence or all-cause mortality are retrospectively collected from the&#xD;
      electronic patient journal system (EPIC/OPUS).&#xD;
&#xD;
      Blood samples of creatinine and C-Reactive Protein are collected with one baseline&#xD;
      preoperative sample (within 30 days before the operation) and postoperative day 1 to 7. Most&#xD;
      patients will be discharged 2 to 3 days after the operation. Creatinine will be analyzed as a&#xD;
      delta value of the baseline and the postoperative maximum serum creatinine value. In the&#xD;
      analysis of CRP the investigators will compare the postoperative in-hospital peak-value.&#xD;
&#xD;
      Troponine I is a biomarker of MINS (myocardial injury after non-cardiac surgery) that was&#xD;
      measured in the study period on postoperative day 1 to 4 or until discharge. Troponine I&#xD;
      values will be categorized in &lt; 15, 15-45 and &gt;45.&#xD;
&#xD;
      Study outcome The primary outcome measure is changes in opioid use between the two groups&#xD;
      (+/- NSAID), calculated as oral morphine equivalent (omeq) doses in mg. The secondary outcome&#xD;
      measures are length of stay, postoperative medical complications within 30 days, changes in&#xD;
      postoperative troponine I and creatinine, colorectal cancer recurrence and all-cause&#xD;
      mortality.&#xD;
&#xD;
      A subgroup analysis of the primary outcome with patients who underwent a laparoscopic&#xD;
      resection (including robotic assisted surgery) as well as a subgroup analysis excluding all&#xD;
      patients with a surgical complication will be done.&#xD;
&#xD;
      Power calculation The sample size calculation was based on non-parametric testing regarding&#xD;
      the primary outcome. The minimally clinically relevant difference in opioid consumption&#xD;
      between the two groups was estimated to 25 % with a standarddeviation of 37.5 oral morphine&#xD;
      equivalent (omeq). To detect a difference with a power of 80 % and an error alpha of 0.05 the&#xD;
      total sample size was estimated to 502 patients - 251 patients in each group.&#xD;
&#xD;
      Statistical analyses Data will be analyzed using non-parametric tests. For dichotomous data&#xD;
      Chi-square/Fishers exact test will be used and quantitative data will be analyzed using the&#xD;
      Mann-Whitney test.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2015</start_date>
  <completion_date type="Actual">December 31, 2017</completion_date>
  <primary_completion_date type="Actual">December 31, 2017</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>4 Years</target_duration>
  <primary_outcome>
    <measure>Postoperative opioid-consumption</measure>
    <time_frame>from the day of operation and until discharge (median 3 days)</time_frame>
    <description>potential changes in the total p.n. use of opioids measured in oral morphine equivalent doses in mg (omeq)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Postoperative renal impact</measure>
    <time_frame>from the day of operation and 7 days postoperatively or until discharge.</time_frame>
    <description>Potential differences in postoperative peak serum - creatinine compared to preoperative serum-creatinine (&lt; 30 days preoperative)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative cardiac impact</measure>
    <time_frame>was measured on day 1 to 4 after surgery or intil discharge.</time_frame>
    <description>Potential differences in serum Troponine I as a sign of MINS (myocardial injury after non-cardiac surgery).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Colorectal cancer recurrence</measure>
    <time_frame>120 days after surgery and until data collection.</time_frame>
    <description>A recurrence of colorectal cancer 120 days after primary surgery registered in the Danish national patient register</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>mortality</measure>
    <time_frame>From the day of operation and 3 to 5 years after (at the time of data collection).</time_frame>
    <description>all-cause mortality</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">502</enrollment>
  <condition>Colo-rectal Cancer</condition>
  <arm_group>
    <arm_group_label>+NSAIDs</arm_group_label>
    <description>Patients undergoing elective colorectal cancer resection before april 1st 2016 were treated with paracetamol tablets 1000 mg and ibuprofen tablets 400 mg four times a day from the day of the operation and until discharge.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>-NSAIDs</arm_group_label>
    <description>Patients undergoing elective colorectal cancer resection from april 1st 2016 were only treated with paracetamol tablets 1000 mg four times a day from the day of the operation and until discharge.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NSAID</intervention_name>
    <description>no other intervention than described in the groups.</description>
    <arm_group_label>+NSAIDs</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients undergoing elective laparoscopic colorectal cancer resection at Zealand University&#xD;
        Hospital, Denmark before and after 1st. of April 2016 are eligible for the study. Patients&#xD;
        with a preoperative use of opioids within the last 3 months, undergoing a palliative&#xD;
        resection or had a surgical complication leading to reoperation in general anesthesia will&#xD;
        be excluded. Palliative resection is defined as patients with symptomatic metastatic&#xD;
        colorectal cancer that undergoes resection of the primary tumor with the aim to relieve&#xD;
        symptoms such as obstruction, bleeding or perforation.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  adults undergoing elective colorectal cancer resection before and after April 1st 2016&#xD;
             at Zealand University Hospital, Denmark.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  palliative resection&#xD;
&#xD;
          -  preoperative use of opioids within the last 3 months&#xD;
&#xD;
          -  patients with a surgical complication requiring re-operation in general anesthesia.&#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>Ismail Gögenur, Med.Sc.D</last_name>
    <role>Study Chair</role>
    <affiliation>Professor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Zealand University Hospital</name>
      <address>
        <city>Køge</city>
        <state>Zealand</state>
        <zip>DK-4600</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <reference>
    <citation>Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006 Jun 3;332(7553):1302-8. doi: 10.1136/bmj.332.7553.1302.</citation>
    <PMID>16740558</PMID>
  </reference>
  <reference>
    <citation>Coxib and traditional NSAID Trialists' (CNT) Collaboration; Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, Bombardier C, Cannon C, Farkouh ME, FitzGerald GA, Goss P, Halls H, Hawk E, Hawkey C, Hennekens C, Hochberg M, Holland LE, Kearney PM, Laine L, Lanas A, Lance P, Laupacis A, Oates J, Patrono C, Schnitzer TJ, Solomon S, Tugwell P, Wilson K, Wittes J, Baigent C. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013 Aug 31;382(9894):769-79. doi: 10.1016/S0140-6736(13)60900-9. Epub 2013 May 30.</citation>
    <PMID>23726390</PMID>
  </reference>
  <reference>
    <citation>Ungprasert P, Cheungpasitporn W, Crowson CS, Matteson EL. Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury: A systematic review and meta-analysis of observational studies. Eur J Intern Med. 2015 May;26(4):285-91. doi: 10.1016/j.ejim.2015.03.008. Epub 2015 Apr 8.</citation>
    <PMID>25862494</PMID>
  </reference>
  <reference>
    <citation>Klein M, Gogenur I, Rosenberg J. Postoperative use of non-steroidal anti-inflammatory drugs in patients with anastomotic leakage requiring reoperation after colorectal resection: cohort study based on prospective data. BMJ. 2012 Sep 26;345:e6166. doi: 10.1136/bmj.e6166.</citation>
    <PMID>23015299</PMID>
  </reference>
  <reference>
    <citation>Bakker N, Deelder JD, Richir MC, Cakir H, Doodeman HJ, Schreurs WH, Houdijk AP. Risk of anastomotic leakage with nonsteroidal anti-inflammatory drugs within an enhanced recovery program. J Gastrointest Surg. 2016 Apr;20(4):776-82. doi: 10.1007/s11605-015-3010-1. Epub 2015 Nov 4.</citation>
    <PMID>26536884</PMID>
  </reference>
  <reference>
    <citation>Dulai PS, Singh S, Marquez E, Khera R, Prokop LJ, Limburg PJ, Gupta S, Murad MH. Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis. BMJ. 2016 Dec 5;355:i6188. doi: 10.1136/bmj.i6188.</citation>
    <PMID>27919915</PMID>
  </reference>
  <reference>
    <citation>Bernardi MH, Schmidlin D, Schiferer A, Ristl R, Neugebauer T, Hiesmayr M, Druml W, Lassnigg A. Impact of preoperative serum creatinine on short- and long-term mortality after cardiac surgery: a cohort study. Br J Anaesth. 2015 Jan;114(1):53-62. doi: 10.1093/bja/aeu316. Epub 2014 Sep 19.</citation>
    <PMID>25240162</PMID>
  </reference>
  <reference>
    <citation>Lassnigg A, Schmid ER, Hiesmayr M, Falk C, Druml W, Bauer P, Schmidlin D. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure? Crit Care Med. 2008 Apr;36(4):1129-37. doi: 10.1097/CCM.0b013e318169181a.</citation>
    <PMID>18379238</PMID>
  </reference>
  <reference>
    <citation>Schack A, Fransgaard T, Klein MF, Gogenur I. Perioperative Use of Nonsteroidal Anti-inflammatory Drugs Decreases the Risk of Recurrence of Cancer After Colorectal Resection: A Cohort Study Based on Prospective Data. Ann Surg Oncol. 2019 Nov;26(12):3826-3837. doi: 10.1245/s10434-019-07600-8. Epub 2019 Jul 16.</citation>
    <PMID>31313040</PMID>
  </reference>
  <reference>
    <citation>Devereaux PJ, Duceppe E, Guyatt G, Tandon V, Rodseth R, Biccard BM, Xavier D, Szczeklik W, Meyhoff CS, Vincent J, Franzosi MG, Srinathan SK, Erb J, Magloire P, Neary J, Rao M, Rahate PV, Chaudhry NK, Mayosi B, de Nadal M, Iglesias PP, Berwanger O, Villar JC, Botto F, Eikelboom JW, Sessler DI, Kearon C, Pettit S, Sharma M, Connolly SJ, Bangdiwala SI, Rao-Melacini P, Hoeft A, Yusuf S; MANAGE Investigators. Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial. Lancet. 2018 Jun 9;391(10137):2325-2334. doi: 10.1016/S0140-6736(18)30832-8. Erratum In: Lancet. 2018 Jul 7;392(10141):30.</citation>
    <PMID>29900874</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 17, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 26, 2020</study_first_posted>
  <last_update_submitted>June 22, 2020</last_update_submitted>
  <last_update_submitted_qc>June 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 26, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Zealand University Hospital</investigator_affiliation>
    <investigator_full_name>Stine Turino</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 20, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT04448652/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04448652
org study id: nsaid_syt
secondary id: 18-000315/115
nct id: NCT04448652
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patients undergoing an operation for colorectal cancer are normally treated with
      non-steroid-anti-inflammatory-drugs (NSAIDs) e.g. ibuprofen as pain medication after the
      operation. It is well known that NSAIDs can be harmful to kidney-and heart patients and some
      studies also have shown an increased risc of surgical complications after treatment with
      NSAIDs. On the other hand recent studies have found a preventive effect of NSAIDs on
      colorectal cancer recurrence thus leaving the colorectal surgeon in doubt whether NSAIDs are
      beneficial or harmful to colorectal cancer patients.

      In the department of colorectal cancer surgery at Zealand University Hospital it was decided
      to leave out NSAIDs from the 1st of april 2016. This study will investigate if there is a
      change in consumption of opioids before and after omission of NSAIDs. This will be an
      important finding because opioids also have harmful side-effects as well as a risk of
      addiction. The investigators will also compare the blood samples and see if there is signs of
      impaired renal and cardiac function in the group that was treated with NSAIDs. Finally the
      long term outcomes will be investigated such as cancer recurrence and death in the two
      groups.
Background:

      Many standard analgesic regimens after colorectal cancer surgery includes a NSAID in
      combination with paracetamol and other non-opioid analgesics. Concerns about a risk of
      cardiovascular and renal impairment and the possible association with anastomotic leaks have
      questioned the rationale of NSAID use in the postoperative period and the need for possible
      alternatives. In the department of colorectal cancer -surgery of Zealand University Hospital
      it was decided to remove NSAIDs from the standard analgesic package from 1th of April 2016
      without other analgesic substitution. This change might imply deterioration of the enhanced
      recovery program with an increase in the use of opioids and side effects that might cause a
      longer length of stay. In addition, recent studies are relaunching ibuprofen as a
      chemo-preventive of colorectal cancer thus leaving the colorectal surgeon in doubt whether
      NSAIDs are beneficial or harmful to colorectal cancer patients.

      Objective:

      The aim of the present study is to investigate the short- and long-term outcomes before (+
      ibuprofen) and after (- ibuprofen) April 1 st 2016.

      Methods Design A prospective, consecutive single-center cohort-study. Study population
      Patients undergoing elective laparoscopic colorectal cancer resection at Zealand University
      Hospital, before and after 1st. of April 2016 are eligible for the study. Patients with a
      preoperative use of opioids within the last 3 months, undergoing a palliative resection or
      had a surgical complication leading to reoperation in general anesthesia will be excluded.
      Palliative resection is defined as patients with symptomatic metastatic colorectal cancer
      that undergoes resection of the primary tumor with the aim to relieve symptoms such as
      obstruction, bleeding or perforation.

      Before April 1st. 2016 all patients, regardless of cardiovascular morbidity or kidney
      disease, received ibuprofen 400 mg in combination with paracetamol 1000 mg four times a day
      in the postoperative period and until admission. After April 1st the patients only received
      paracetamol. If the standard analgesic regimen was insufficient, patients in both groups were
      treated with intravenous, subcutaneous or oral opioids defined as drugs within the ACT-code
      (Anatomical Therapeutic Chemical Classification System) N02A. The department has a
      well-implemented Enhanced Recovery After Surgery (ERAS) program with a standardized
      management of the perioperative course and discharge with no other changes in the program in
      the study period.

      Demographic and perioperative data including length of stay and postoperative complications
      within 30 days will be collected from the national prospective database of the Danish
      Colorectal Cancer Group. According to the exclusion criteria all patients with a registered
      surgical complication clavien dindo ≥3b will be excluded. The postoperative medical
      complications are categorized in the database in: Stroke, acute myocardial infarction,
      aspiration, pneumonia, heart failure, lung embolism, respiratory insufficiency, kidney
      failure, sepsis, deep venous thrombosis, arterial embolism and "other medical complication".
      The medical complications are also graded according to the clavien-dindo classification
      system. Daily postoperative opioid consumption until discharge, readmissions within 30 days,
      colorectal cancer recurrence or all-cause mortality are retrospectively collected from the
      electronic patient journal system (EPIC/OPUS).

      Blood samples of creatinine and C-Reactive Protein are collected with one baseline
      preoperative sample (within 30 days before the operation) and postoperative day 1 to 7. Most
      patients will be discharged 2 to 3 days after the operation. Creatinine will be analyzed as a
      delta value of the baseline and the postoperative maximum serum creatinine value. In the
      analysis of CRP the investigators will compare the postoperative in-hospital peak-value.

      Troponine I is a biomarker of MINS (myocardial injury after non-cardiac surgery) that was
      measured in the study period on postoperative day 1 to 4 or until discharge. Troponine I
      values will be categorized in < 15, 15-45 and >45.

      Study outcome The primary outcome measure is changes in opioid use between the two groups
      (+/- NSAID), calculated as oral morphine equivalent (omeq) doses in mg. The secondary outcome
      measures are length of stay, postoperative medical complications within 30 days, changes in
      postoperative troponine I and creatinine, colorectal cancer recurrence and all-cause
      mortality.

      A subgroup analysis of the primary outcome with patients who underwent a laparoscopic
      resection (including robotic assisted surgery) as well as a subgroup analysis excluding all
      patients with a surgical complication will be done.

      Power calculation The sample size calculation was based on non-parametric testing regarding
      the primary outcome. The minimally clinically relevant difference in opioid consumption
      between the two groups was estimated to 25 % with a standarddeviation of 37.5 oral morphine
      equivalent (omeq). To detect a difference with a power of 80 % and an error alpha of 0.05 the
      total sample size was estimated to 502 patients - 251 patients in each group.

      Statistical analyses Data will be analyzed using non-parametric tests. For dichotomous data
      Chi-square/Fishers exact test will be used and quantitative data will be analyzed using the
      Mann-Whitney test.
observational model: Cohort
time perspective: Prospective
measure: Postoperative opioid-consumption
time frame: from the day of operation and until discharge (median 3 days)
description: potential changes in the total p.n. use of opioids measured in oral morphine equivalent doses in mg (omeq)
measure: Postoperative renal impact
time frame: from the day of operation and 7 days postoperatively or until discharge.
description: Potential differences in postoperative peak serum - creatinine compared to preoperative serum-creatinine (< 30 days preoperative)
measure: Postoperative cardiac impact
time frame: was measured on day 1 to 4 after surgery or intil discharge.
description: Potential differences in serum Troponine I as a sign of MINS (myocardial injury after non-cardiac surgery).
measure: Colorectal cancer recurrence
time frame: 120 days after surgery and until data collection.
description: A recurrence of colorectal cancer 120 days after primary surgery registered in the Danish national patient register
measure: mortality
time frame: From the day of operation and 3 to 5 years after (at the time of data collection).
description: all-cause mortality
arm group label: +NSAIDs
description: Patients undergoing elective colorectal cancer resection before april 1st 2016 were treated with paracetamol tablets 1000 mg and ibuprofen tablets 400 mg four times a day from the day of the operation and until discharge.
arm group label: -NSAIDs
description: Patients undergoing elective colorectal cancer resection from april 1st 2016 were only treated with paracetamol tablets 1000 mg four times a day from the day of the operation and until discharge.
intervention type: Drug
intervention name: NSAID
description: no other intervention than described in the groups.
arm group label: +NSAIDs
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ismail Gögenur, Med.Sc.D
role: Study Chair
affiliation: Professor
facility: 
country: Denmark
citation: Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006 Jun 3;332(7553):1302-8. doi: 10.1136/bmj.332.7553.1302.
PMID: 16740558
citation: Coxib and traditional NSAID Trialists' (CNT) Collaboration; Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, Bombardier C, Cannon C, Farkouh ME, FitzGerald GA, Goss P, Halls H, Hawk E, Hawkey C, Hennekens C, Hochberg M, Holland LE, Kearney PM, Laine L, Lanas A, Lance P, Laupacis A, Oates J, Patrono C, Schnitzer TJ, Solomon S, Tugwell P, Wilson K, Wittes J, Baigent C. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013 Aug 31;382(9894):769-79. doi: 10.1016/S0140-6736(13)60900-9. Epub 2013 May 30.
PMID: 23726390
citation: Ungprasert P, Cheungpasitporn W, Crowson CS, Matteson EL. Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury: A systematic review and meta-analysis of observational studies. Eur J Intern Med. 2015 May;26(4):285-91. doi: 10.1016/j.ejim.2015.03.008. Epub 2015 Apr 8.
PMID: 25862494
citation: Klein M, Gogenur I, Rosenberg J. Postoperative use of non-steroidal anti-inflammatory drugs in patients with anastomotic leakage requiring reoperation after colorectal resection: cohort study based on prospective data. BMJ. 2012 Sep 26;345:e6166. doi: 10.1136/bmj.e6166.
PMID: 23015299
citation: Bakker N, Deelder JD, Richir MC, Cakir H, Doodeman HJ, Schreurs WH, Houdijk AP. Risk of anastomotic leakage with nonsteroidal anti-inflammatory drugs within an enhanced recovery program. J Gastrointest Surg. 2016 Apr;20(4):776-82. doi: 10.1007/s11605-015-3010-1. Epub 2015 Nov 4.
PMID: 26536884
citation: Dulai PS, Singh S, Marquez E, Khera R, Prokop LJ, Limburg PJ, Gupta S, Murad MH. Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis. BMJ. 2016 Dec 5;355:i6188. doi: 10.1136/bmj.i6188.
PMID: 27919915
citation: Bernardi MH, Schmidlin D, Schiferer A, Ristl R, Neugebauer T, Hiesmayr M, Druml W, Lassnigg A. Impact of preoperative serum creatinine on short- and long-term mortality after cardiac surgery: a cohort study. Br J Anaesth. 2015 Jan;114(1):53-62. doi: 10.1093/bja/aeu316. Epub 2014 Sep 19.
PMID: 25240162
citation: Lassnigg A, Schmid ER, Hiesmayr M, Falk C, Druml W, Bauer P, Schmidlin D. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure? Crit Care Med. 2008 Apr;36(4):1129-37. doi: 10.1097/CCM.0b013e318169181a.
PMID: 18379238
citation: Schack A, Fransgaard T, Klein MF, Gogenur I. Perioperative Use of Nonsteroidal Anti-inflammatory Drugs Decreases the Risk of Recurrence of Cancer After Colorectal Resection: A Cohort Study Based on Prospective Data. Ann Surg Oncol. 2019 Nov;26(12):3826-3837. doi: 10.1245/s10434-019-07600-8. Epub 2019 Jul 16.
PMID: 31313040
citation: Devereaux PJ, Duceppe E, Guyatt G, Tandon V, Rodseth R, Biccard BM, Xavier D, Szczeklik W, Meyhoff CS, Vincent J, Franzosi MG, Srinathan SK, Erb J, Magloire P, Neary J, Rao M, Rahate PV, Chaudhry NK, Mayosi B, de Nadal M, Iglesias PP, Berwanger O, Villar JC, Botto F, Eikelboom JW, Sessler DI, Kearon C, Pettit S, Sharma M, Connolly SJ, Bangdiwala SI, Rao-Melacini P, Hoeft A, Yusuf S; MANAGE Investigators. Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial. Lancet. 2018 Jun 9;391(10137):2325-2334. doi: 10.1016/S0140-6736(18)30832-8. Erratum In: Lancet. 2018 Jul 7;392(10141):30.
PMID: 29900874
responsible party type: Principal Investigator
investigator affiliation: Zealand University Hospital
investigator full name: Stine Turino
investigator title: Principal investigator
mesh term: Colorectal Neoplasms
provided document: 