<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/NCT04412694</url>
  </required_header>
  <id_info>
    <org_study_id>MULODZ nr RNN/133/20/KE</org_study_id>
    <nct_id>NCT04412694</nct_id>
  </id_info>
  <brief_title>The Effect of Preoperative Oral Dexamethasone Supplementation on the Outcome of Thyroidectomised Patients.</brief_title>
  <acronym>Dexa</acronym>
  <official_title>The Impact of Preoperative Oral Dexamethasone Supplementation on the Biochemical Parameters and Results of Surgical Treatment in Patients With Nontoxic Multinodular Goiter Undergoing Total Thyroidectomy.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Lodz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Lodz</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>
      Glucocorticoids are well known for their analgesic, anti-inflammatory, immunomodulatory and&#xD;
      anti-emetic effects. Recovery time after thyroid surgery may depend on several factors, such&#xD;
      as postoperative pain, nausea and vomiting, postoperative sore throat, voice disorders and&#xD;
      symptomatic hypocalcaemia (low serum calcium level). However, there is little information in&#xD;
      the literature about the preventive use of glucocorticosteroids in patients undergoing&#xD;
      thyroid surgery. The aim of the study is to evaluate the clinical impact of preoperative oral&#xD;
      dexamethasone supplementation on the surgical outcome in patients with multinodular goiter&#xD;
      undergoing total thyroidectomy. Patients will be assigned to the supplementation group and&#xD;
      the placebo group. In the supplementation group 8mg of dexamethasone will be administered&#xD;
      orally one hour before surgery. In the postoperative period, the frequency and intensity of&#xD;
      pain, nausea, vomiting, sore throat and hoarseness will be assessed. The incidence of&#xD;
      symptoms of hypocalcaemia will also be evaluted. Preoperative and postoperative levels of&#xD;
      vitamin D, cytokines, acute phase proteins and substances related to calcium metabolism will&#xD;
      be measured in the blood. Cytokines levels in drainage fluid will also be assessed. The main&#xD;
      hypothesis of the study is that in patients with supplementation postoperative discomfort and&#xD;
      decrease in serum calcium and parathormone level and hypocalcemic symptoms will be less&#xD;
      severe and the levels of proinflammatory substances will be decreased.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recovery time after thyroid surgery may depend on several factors, such as postoperative&#xD;
      pain, nausea and vomiting, postoperative sore throat, phonation disorders associated with&#xD;
      recurrent laryngeal nerve palsy, and symptomatic postoperative hypocalcaemia associated with&#xD;
      postoperative hypoparathyroidism.&#xD;
&#xD;
      Glucocorticoids are well known for their analgesic, anti-inflammatory, immunomodulatory and&#xD;
      anti-emetic effects. However, there is little information in the literature on the&#xD;
      prophylactic use of glucocorticosteroids in patients undergoing thyroid surgery. In some&#xD;
      previous studies, preoperative intravenous dexamethasone supplementation was associated with&#xD;
      a reduced incidence of postoperative laryngeal nerve palsy, postoperative hypoparathyroidism,&#xD;
      and with less severe postoperative pain, postoperative sore throat, nausea and vomiting.&#xD;
      Patients receiving supplementation also had decreased levels of inflammatory biochemical&#xD;
      parameters and proinflammatory cytokines.&#xD;
&#xD;
      Vitamin D deficiency is widespread in Poland. Vitamin D status has an impact on the&#xD;
      postoperative complications in surgical patients. In previous study serum 25-hydroxyvitamin D&#xD;
      is also suggested as a negative acute phase reactant, which has implications for acute and&#xD;
      chronic inflammatory diseases. According to the authors, serum 25-hydroxyvitamin D level is&#xD;
      an unreliable biomarker of vitamin D status after acute inflammatory insult.&#xD;
&#xD;
      In the early stages of inflammation, phagocytic cells and endothelium secrete proinflammatory&#xD;
      cytokines, which include: interleukins: IL-1 α / β, IL-6, IL-8, TNF. The antagonistic group&#xD;
      is anti-inflammatory cytokines, which include interleukins: IL-4, -5, -10, -13, produced by&#xD;
      Th2 lymphocytes. These cytokines reduce the amount of interleukins secreted by Th1&#xD;
      lymphocytes.&#xD;
&#xD;
      Changes in the levels of proinflammatory and anti-inflammatory cytokines in the postoperative&#xD;
      period were found in studies related to the assessment of surgical trauma. Pro-inflammatory&#xD;
      interleukin 1 and interleukin 6 play an important role in many biological processes such as&#xD;
      inflammation, sepsis and wound healing. Interleukin 6 expression is proportional to the&#xD;
      extent of the surgical trauma. In turn, interleukin 10 is known as a cytokine that inhibits&#xD;
      cytokine synthesis. Is one of the strongest immunosuppressive agents.&#xD;
&#xD;
      The aim of my study is to evaluate the impact of preoperative oral dexamethasone&#xD;
      supplementation on the biochemical parameters and results of surgical treatment in patients&#xD;
      with nontoxic multinodular goiter undergoing total thyroidectomy.&#xD;
&#xD;
      Patients admitted to the Department of General and Oncological Surgery, Medical University of&#xD;
      Lodz with preoperative diagnosis of nontoxic multinodular goitre undergoing total&#xD;
      thyroidectomy will be inculded to the study.&#xD;
&#xD;
      After obtaining written informed consent from all participants during a preoperative visit,&#xD;
      they will be randomized to the supplementation group and the placebo group. The study will be&#xD;
      a prospective, placebo-controlled and double-blind (for patient and surgeon) research.&#xD;
&#xD;
      Intervention: In the supplementation group a single dose of 8mg of dexamethasone will be&#xD;
      given orally one hour before surgery (Dexamethasone Krka tablets (8mg), Warsaw, Poland). In&#xD;
      the placebo group patients will receive a single tablet of sweetener one hour before&#xD;
      operation (Clio tablets, sweetener with a dispenser, Instantina GES, Vienna, Austria).&#xD;
&#xD;
      Preoperatively in the group of all enrolled patients (in the supplementation group and in the&#xD;
      placebo group) following tests will be measured in serum: blood count, calcium, inorganic&#xD;
      phosphates, albumin, alkaline phosphatase, C reactive protein, procalcitonin,&#xD;
      25-hydroxyvitamin D, fibrinogen, parathormone, magnesium, interleukin 1β, interleukin 6,&#xD;
      interleukin 10, thyroid stimulating hormone, free thyroxine, free triiodothyronine.&#xD;
&#xD;
      Total thyroidectomies with routine identification of the recurrent laryngeal nerves and&#xD;
      parathyroid glands via a transverse cervicotomy under general anaesthesia will be performed&#xD;
      by 3 experienced surgeons.&#xD;
&#xD;
      During the total thyroidectomy the number of parathyroid glands found intraoperatively will&#xD;
      be registered.&#xD;
&#xD;
      At 6 hour after surgery in the group of all enrolled patients following tests will be&#xD;
      measured in serum: blood count, calcium, inorganic phosphates, albumin, alkaline phosphatase,&#xD;
      C reactive protein, procalcitonin, 25-hydroxyvitamin D, fibrinogen, parathormone, magnesium.&#xD;
      In addiction, at 6 hour after surgery the incidence and intensity of symptomatic&#xD;
      hypocalcaemia, postoperative pain (according to VAS scale), postoperative nausea and&#xD;
      vomiting, postoperative sore throat and hoarseness will be evaluated.&#xD;
&#xD;
      At 24 hour after surgery in the group of all enrolled patients following tests will be&#xD;
      measured in serum: blood count, calcium, inorganic phosphates, albumin, alkaline phosphatase,&#xD;
      C reactive protein, procalcitonin, 25-hydroxyvitamin D, fibrinogen, parathormone, magnesium,&#xD;
      interleukin 1β, interleukin 6, interleukin 10. Additionally, the level of interleukin 1β,&#xD;
      interleukin 6 and interleukin 10 will be evaluated in drainage fluid. In addiction, at 24&#xD;
      hour after surgery the incidence and intensity of symptomatic hypocalcaemia, postoperative&#xD;
      pain (according to Visual Analogue Scale - VAS scale), postoperative nausea and vomiting,&#xD;
      postoperative sore throat and hoarseness will be evaluated.&#xD;
&#xD;
      The laboratory parameters will be determined by electrochemiluminescence on the Cobas E411&#xD;
      analyzer and spectrophotometric method on the AU680, Beckman Coulter analyzer.&#xD;
      25-hydroxyvitamin D levels will be measured using the chemiluminescent microparticle&#xD;
      immunoassay (CMIA) (Architect 25-OHD). Interleukins levels will be determined by enzyme&#xD;
      immunoassay method (EIA) (DGR Medtek) on ElizaMat 2 X analyzer.&#xD;
&#xD;
      Hypocalcemic symptoms will be categorized as mild (a tingling sensation and numbness of the&#xD;
      hands or feet and perioral numbness) or severe (a positive Chvostek sign, Trousseau sign,&#xD;
      tetany, and carpopedal spasms).&#xD;
&#xD;
      Postoperative hypocalcaemia will be defined as corrected calcium levels &lt;2.0 mmol/l, even if&#xD;
      recorded in one measurement only.&#xD;
&#xD;
      In both groups participants who will develop postoperative hypoparathyroidism (parathormone&#xD;
      level &lt;1.6 pmol/l at 6 or 24 hour after surgery) or symptomatic hypocalcaemia during&#xD;
      hospitalisation will be treated with oral calcium (3 g/d - taken 1 g every 8 hours) and&#xD;
      vitamin D derivatives (1 ug/d alfacalcidol taken once).&#xD;
&#xD;
      Intravenous calcium gluconate will be administered if symptoms persist despite oral&#xD;
      supplementation.&#xD;
&#xD;
      Patients with symptomatic hypocalcaemia will receive supplementation until the symptoms&#xD;
      subside. The treatment will be extended to 6 weeks in patients with hypoparathyroidism on the&#xD;
      day of discharge.&#xD;
&#xD;
      The data will be statistically analysed. The main hypothesis of the study is that in patients&#xD;
      with supplementation postoperative discomfort and decrease in serum calcium and parathormone&#xD;
      level and hypocalcemic symptoms will be less severe and the levels of proinflammatory&#xD;
      substances will be decreased. Vitamin D deficiency is probably common in operated patients&#xD;
      and postoperative 25-hydroxyvitamin D levels are lower than those measured preoperatively.&#xD;
&#xD;
      The use of oral dexamethasone might be an effective strategy of prevention of complications&#xD;
      after total thyroidectomy.&#xD;
&#xD;
      To the best of our knowledge, this is a pioneering study assessing the usefulness of&#xD;
      preventive oral dexamethasone supplementation before total thyroidectomy in homogeneous group&#xD;
      of patients with nontoxic multinodular goiter undergoing total thyroidectomy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">September 2022</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>
    <intervention_model_description>Patients will be randomly assigned (coin toss) to the supplementation group (preoperative oral supplementation of dexamethasone (8mg in one dose) taken one hour before surgery) and to the placebo group (preoperative oral supplementation of sweetener taken one hour before surgery).</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Postoperative hypocalcaemia</measure>
    <time_frame>preoperatively and at 6 and 24 hour after surgery</time_frame>
    <description>To evaluate the incidence of laboratory hypocalcaemia (corrected calcium serum level &lt;2.0 mmol/l), the change in calcium levels and symptomatic hypocalcaemia in the postoperative period in the supplementation group and in the placebo group.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Postoperative hypoparathyroidism</measure>
    <time_frame>preoperatively and at 6 and 24 hour after surgery</time_frame>
    <description>To evaluate the incidence of hypoparathyroidism (parathormone serum level &lt;1.6 pmol/l) and the change in parathormone levels in the postoperative period in the supplementation group and in the placebo group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Postoperative pain</measure>
    <time_frame>at 6 and 24 hour after surgery</time_frame>
    <description>To evaluate the intensity of postoperative pain according to Visual Analogue Scale (VAS scale) in the postoperative period in the supplementation group and in the placebo group. Minimum value is 0 (no pain) and maximum value is 10 (the worst possible pain). Higher scores mean a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative nausea on a verbal rating scale</measure>
    <time_frame>at 6 and 24 hour after surgery</time_frame>
    <description>To evaluate the incidence and the intensity of postoperative nausea in the postoperative period in the supplementation group and in the placebo group. The intensity of nausea will be rated on a verbal rating scale based on verbal responses of the patient to questions: 0 - no nausea; 1 - mild nausea (1 episode of nausea); 2 - moderate nausea (2 or 3 episodes of nausea ); and 3 - severe nausea (&gt;3 episodes of nausea ). Higher scores mean a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative vomiting on a verbal rating scale</measure>
    <time_frame>at 6 and 24 hour after surgery</time_frame>
    <description>To evaluate the incidence and the intensity of postoperative vomiting in the postoperative period in the supplementation group and in the placebo group.The intensity of vomiting will be rated on a verbal rating scale based on verbal responses of the patient to questions: 0 - no episodes of vomiting; 1 - mild vomiting (1 episode of vomiting); 2 - moderate vomiting (2 or 3 episodes of vomiting); and 3 - severe vomiting (&gt;3 episodes of vomiting).Higher scores mean a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative sore throat on a verbal rating scale</measure>
    <time_frame>at 6 and 24 hour after surgery</time_frame>
    <description>To evaluate the incidence and the intensity of postoperative sore throat in the postoperative period in the supplementation group and in the placebo group. Postoperative sore throat will be defined as discomfort at larynx or pharynx at rest and during swallowing after surgery. The intensity of sore throat will be rated on a verbal rating scale based on verbal responses of the patient to questions: 0 - none; 1 - mild sore throat (less severe than with a cold); 2 - moderate sore throat (similar with a cold); and 3 - severe sore throat (more severe than with a cold). Higher scores mean a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative hoarseness on a verbal rating scale</measure>
    <time_frame>at 6 and 24 hour after surgery</time_frame>
    <description>To evaluate the incidence and the intensity of postoperative hoarseness in the postoperative period in the supplementation group and in the placebo group. The intensity of hoarseness will be rated on a verbal rating scale based on verbal responses of the patient to questions: 0 - none; 1 - mild hoarseness (noticed by the patient only); 2 - severe hoarseness (obvious to observer); 3 - aphonia (silence of voice). Higher scores mean a worse outcome.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Cytokines in serum</measure>
    <time_frame>preoperatively and at 6 and 24 hour after surgery</time_frame>
    <description>To evaluate the serum levels of cytokines such as interleukin 1β, interleukin 6, interleukin 10 and the change in cytokines levels in the postoperative period in the supplementation group and in the placebo group.</description>
  </other_outcome>
  <other_outcome>
    <measure>Cytokines in drain fluid</measure>
    <time_frame>at 24 hour after surgery</time_frame>
    <description>To evaluate the levels of cytokines such as interleukin 1β, interleukin 6, interleukin 10 in the drain fluid in the postoperative period in the supplementation group and in the placebo group.</description>
  </other_outcome>
  <other_outcome>
    <measure>Calcium phosphate homeostasis</measure>
    <time_frame>preoperatively and at 6 and 24 hour after surgery</time_frame>
    <description>To evaluate the serum levels of alkaline phosphatase,inorganic phosphates and magnesium and the change in their levels in the postoperative period in the supplementation group and in the placebo group.</description>
  </other_outcome>
  <other_outcome>
    <measure>Vitamin D</measure>
    <time_frame>preoperatively and at 6 and 24 hour after surgery</time_frame>
    <description>To evaluate the levels of 25-hydroxyvitamin D in the preoperative and postoperative period and the change in its levels in the supplementation group and in the placebo group. To evaluate the incidence of vitamin D deficiency in the group of operated patients.</description>
  </other_outcome>
  <other_outcome>
    <measure>Acute phase proteins</measure>
    <time_frame>preoperatively and at 6 and 24 hour after surgery</time_frame>
    <description>To evaluate the serum levels of albumin, C reactive protein, procalcitonin and fibrinogen and the change in their levels in the postoperative period in the supplementation group and in the placebo group.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Hypocalcemia</condition>
  <condition>Vitamin D Deficiency</condition>
  <condition>Postoperative Complications</condition>
  <condition>Postoperative Nausea</condition>
  <condition>Postoperative Pain</condition>
  <condition>Voice Hoarseness</condition>
  <condition>Hypoparathyroidism Postprocedural</condition>
  <arm_group>
    <arm_group_label>supplementation group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive preoperative oral supplementation of 8mg of dexamethasone (Dexamethasone Krka tablets (8mg), Warsaw, Poland) in a single dose taken once one hour before surgery. At 6 and 24 hour after surgery, clinical and laboratory parameters will be measured and evaluated.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients will receive preoperative oral supplementation of sweetener (Clio tablets, sweetener with a dispenser, Instantina GES, Vienna, Austria) taken once in a single dose one hour before surgery. At 6 and 24 hour after surgery, clinical and laboratory parameters will be measured and evaluated.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone oral tablet 8mg (Dexamethasone Krka tablets(8mg), Warsaw, Poland).</intervention_name>
    <description>Preoperative oral dexamathasone supplementation in a single dose of 8mg.</description>
    <arm_group_label>supplementation group</arm_group_label>
    <other_name>Supplementation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral sweetener (Clio tablets, sweetener with a dispenser, Instantina GES, Vienna, Austria).</intervention_name>
    <description>Preoperative oral supplementation of sweetener in a single dose.</description>
    <arm_group_label>placebo group</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Preoparative blood laboratory tests</intervention_name>
    <description>Preoperative parameters such as blood count, calcium, inorganic phosphates, albumin, alkaline phosphatase, C reactive protein, procalcitonin, 25-hydroxyvitamin D, fibrinogen, parathormone, magnesium, interleukin 1β, interleukin 6, interleukin 10, thyroid stimulating hormone, free thyroxine, free triiodothyronin will be measured in serum.</description>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_label>supplementation group</arm_group_label>
    <other_name>preoperative blood test</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Postoperative laboratory blood tests at 6 hour</intervention_name>
    <description>At 6 hour after surgery such parameters as blood count, calcium, inorganic phosphates, albumin, alkaline phosphatase, C reactive protein, procalcitonin, 25-hydroxyvitamin D, fibrinogen, parathormone, magnesium will be measured in serum.</description>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_label>supplementation group</arm_group_label>
    <other_name>blood tests 6 hour</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Postoperative laboratory blood tests at 24 hour</intervention_name>
    <description>At 24 hour after surgery such parameters as blood count, calcium, inorganic phosphates, albumin, alkaline phosphatase, C reactive protein, procalcitonin, 25-hydroxyvitamin D, fibrinogen, parathormone, magnesium, interleukin 1β, interleukin 6, interleukin 10 will be measured in serum.</description>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_label>supplementation group</arm_group_label>
    <other_name>blood tests 24 hour</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Postoperative laboratory drainage fluid tests at 24 hour</intervention_name>
    <description>At 24 hour after surgery such parameters as interleukin 1β, interleukin 6, interleukin 10 will be measured in drainage fluid.</description>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_label>supplementation group</arm_group_label>
    <other_name>drainage fluid tests 24 hour</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Total thyroidectomy</intervention_name>
    <description>Patients will undergo total thyroidectomy under general anesthesia.</description>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_label>supplementation group</arm_group_label>
    <other_name>thyroidectomy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Symptomatic hypocalcaemia at 6 hour</intervention_name>
    <description>At 6 hour after surgery patients will be assessed for signs of hypocalcaemia.</description>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_label>supplementation group</arm_group_label>
    <other_name>symptoms 6 hour</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Symptomatic hypocalcaemia at 24 hour</intervention_name>
    <description>At 24 hour after surgery patients will be assessed for signs of hypocalcaemia.</description>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_label>supplementation group</arm_group_label>
    <other_name>symptoms 24 hour</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Postoperative pain at 6 hour</intervention_name>
    <description>At 6 hour after surgery the incidence and intensity of postoperative pain will be evaluated according to Visual Analogue Scale (VAS).</description>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_label>supplementation group</arm_group_label>
    <other_name>pain 6 hour</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Postoperative pain at 24 hour</intervention_name>
    <description>At 24 hour after surgery the incidence and intensity of postoperative pain will be evaluated according to Visual Analogue Scale (VAS).</description>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_label>supplementation group</arm_group_label>
    <other_name>pain 24 hour</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Postoperative nausea and vomiting at 6 hour</intervention_name>
    <description>At 6 hour after surgery the incidence and intensity of postoperative nausea and vomiting will be evaluated.</description>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_label>supplementation group</arm_group_label>
    <other_name>nausea 6 hour</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Postoperative nausea and vomiting at 24 hour</intervention_name>
    <description>At 24 hour after surgery the incidence and intensity of postoperative nausea and vomiting will be evaluated.</description>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_label>supplementation group</arm_group_label>
    <other_name>nausea 24 hour</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Postoperative sore throat and hoarseness at 6 hour</intervention_name>
    <description>At 6 hour after surgery the incidence and intensity of postoperative sore throat and hoarseness will be evaluated.</description>
    <arm_group_label>placebo group</arm_group_label>
    <arm_group_label>supplementation group</arm_group_label>
    <other_name>hoarseness 6 hour</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Postoperative sore throat and hoarseness at 24 hour</intervention_name>
    <description>At 24 hour after surgery the incidence and intensity of postoperative sore throat and hoarseness will be evaluated.</description>
    <arm_group_label>placebo group</arm_group_label>
    <other_name>hoarseness 24 hour</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patient's consent&#xD;
&#xD;
          -  adult patients&#xD;
&#xD;
          -  preoperative diagnosis of nontoxic multinodular goiter&#xD;
&#xD;
          -  total thyroidectomy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  lack of patient's consent&#xD;
&#xD;
          -  hyperthyroidism currently or in the past&#xD;
&#xD;
          -  retrosternal goiter&#xD;
&#xD;
          -  thyroid malignanacy or suspected malignant thyroid tumor&#xD;
&#xD;
          -  parathyroids disease&#xD;
&#xD;
          -  malingant tumor in any location currently or in the past&#xD;
&#xD;
          -  state after neck surgery&#xD;
&#xD;
          -  state after radiotherapy&#xD;
&#xD;
          -  bone diseases, osteoporosis&#xD;
&#xD;
          -  sarcoidosis&#xD;
&#xD;
          -  liver failure, hepatitis&#xD;
&#xD;
          -  kidney stones, kidney failure (eGFR&lt;60ml/min/1.73m2)&#xD;
&#xD;
          -  taking nonsteroidal anti-inflammatory drugs&#xD;
&#xD;
          -  steroid treatment&#xD;
&#xD;
          -  stomach and duodenal ulcer disease currently or in the past&#xD;
&#xD;
          -  active infection at the time of the study&#xD;
&#xD;
          -  history of tuberculosis&#xD;
&#xD;
          -  a period of 8 weeks before and 2 weeks after administration of the live vaccine&#xD;
&#xD;
          -  unregulated hypertension&#xD;
&#xD;
          -  diabetes&#xD;
&#xD;
          -  psychiatric disorders&#xD;
&#xD;
          -  glaucoma&#xD;
&#xD;
          -  corneal ulcers or corneal injuries&#xD;
&#xD;
          -  severe heart failure&#xD;
&#xD;
          -  pheochromocytoma&#xD;
&#xD;
          -  myasthenia gravis&#xD;
&#xD;
          -  epilepsy&#xD;
&#xD;
          -  head injury&#xD;
&#xD;
          -  ulcerative colitis&#xD;
&#xD;
          -  diverticulitis&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  breast-feeding&#xD;
&#xD;
          -  hypokalaemia&#xD;
&#xD;
          -  galactose intolerance&#xD;
&#xD;
          -  lactase deficiency&#xD;
&#xD;
          -  dexamethasone allergy, allergic to lactose, allergic to gelatinized starch, allergic&#xD;
             to corn starch, allergic to colloidal anhydrous silica, allergic to magnesium stearate&#xD;
&#xD;
          -  allergic reaction to substances contained in the sweetener: sodium cyclamate, sodium&#xD;
             saccharin, sodium bicarbonate, sodium citrate.&#xD;
&#xD;
          -  taking medications that affect calcium metabolism: anti-resorptive drugs, anabolic&#xD;
             drugs, bisphosphonates, systemic glucocorticosteroids, thiazide diuretics, furosemide,&#xD;
             proton pump inhibitors, antacids containing magnesium or aluminum salts,&#xD;
             cholestyramine, colestipol, paraffin oil, salicylates, estrogen-containing oral&#xD;
             contraceptives (hormonal contraceptives) , preparations containing calcium salts&#xD;
             (regular intake), preparations of vitamin D or its analogues (regular intake)&#xD;
&#xD;
          -  taking medications that increase the side effect of dexamethasone or enter into drug&#xD;
             interactions with dexamethasone: acetazolamide, loop diuretics, thiazide diuretics,&#xD;
             diuretics, amphotericin B, glucocorticosteroids, mineralocorticosteroids,&#xD;
             tetracosactide and laxatives, carbenoxolone, chlorokine, hydroxychlorokine and&#xD;
             meflocin, angiotensin converting enzyme inhibitors, thalidomide, cholinesterase&#xD;
             inhibitors in patients with myasthenia gravis, fluorochonolones, ephedrine,&#xD;
             barbiturates, rifabutin, rifampicin, phenytoin and carbamazepine, aminoglutethimide,&#xD;
             bile acid binding resins, such as cholestyramine, antacids,activated carbon,&#xD;
             antifungal azoles, ketoconazole, HIV protease inhibitors, macrolide antibiotics,&#xD;
             estrogens, anti-tuberculosis drugs (isoniazid), cyclosporin, praziquantel, oral&#xD;
             anticoagulants (coumarin), atropine and other anticholinergic drugs, somatotropin,&#xD;
             protirel.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anna Grzegory, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Lodz, Poland</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Anna Grzegory, MD</last_name>
    <phone>695720008</phone>
    <phone_ext>+48</phone_ext>
    <email>an.grzegory@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of General and Oncological Surgery, Medical University of Lodz</name>
      <address>
        <city>Łódź</city>
        <state>Łódzkie</state>
        <zip>92-213</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna Grzegory, MD</last_name>
      <phone>695720008</phone>
      <email>an.grzegory@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <reference>
    <citation>Schietroma M, Cecilia EM, Carlei F, Sista F, De Santis G, Lancione L, Amicucci G. Dexamethasone for the prevention of recurrent laryngeal nerve palsy and other complications after thyroid surgery: a randomized double-blind placebo-controlled trial. JAMA Otolaryngol Head Neck Surg. 2013 May;139(5):471-8. doi: 10.1001/jamaoto.2013.2821.</citation>
    <PMID>23681030</PMID>
  </reference>
  <reference>
    <citation>Yang C, Jung SM, Bae YK, Park SJ. The effect of ketorolac and dexamethasone on the incidence of sore throat in women after thyroidectomy: a prospective double-blinded randomized trial. Korean J Anesthesiol. 2017 Feb;70(1):64-71. doi: 10.4097/kjae.2017.70.1.64. Epub 2016 Nov 25.</citation>
    <PMID>28184269</PMID>
  </reference>
  <reference>
    <citation>Calkosinski I, Dobrzynski M, Calkosinska M, Seweryn E, Bronowicka-Szydelko A, Dzierzba K, Ceremuga I, Gamian A. [Characterization of an inflammatory response]. Postepy Hig Med Dosw (Online). 2009 Sep 3;63:395-408. Polish.</citation>
    <PMID>19745226</PMID>
  </reference>
  <reference>
    <citation>Waldron JL, Ashby HL, Cornes MP, Bechervaise J, Razavi C, Thomas OL, Chugh S, Deshpande S, Ford C, Gama R. Vitamin D: a negative acute phase reactant. J Clin Pathol. 2013 Jul;66(7):620-2. doi: 10.1136/jclinpath-2012-201301. Epub 2013 Mar 1.</citation>
    <PMID>23454726</PMID>
  </reference>
  <reference>
    <citation>Bennett NT, Schultz GS. Growth factors and wound healing: biochemical properties of growth factors and their receptors. Am J Surg. 1993 Jun;165(6):728-37. doi: 10.1016/s0002-9610(05)80797-4.</citation>
    <PMID>8506974</PMID>
  </reference>
  <reference>
    <citation>Gailit J, Clark RA. Wound repair in the context of extracellular matrix. Curr Opin Cell Biol. 1994 Oct;6(5):717-25. doi: 10.1016/0955-0674(94)90099-x.</citation>
    <PMID>7530463</PMID>
  </reference>
  <reference>
    <citation>Sakamoto K, Arakawa H, Mita S, Ishiko T, Ikei S, Egami H, Hisano S, Ogawa M. Elevation of circulating interleukin 6 after surgery: factors influencing the serum level. Cytokine. 1994 Mar;6(2):181-6. doi: 10.1016/1043-4666(94)90040-x.</citation>
    <PMID>8032001</PMID>
  </reference>
  <reference>
    <citation>Kalayci D, Dikmen B, Kacmaz M, Taspinar V, Ornek D, Turan O. [Plasma levels of interleukin-10 and nitric oxide in response to two different desflurane anesthesia flow rates]. Braz J Anesthesiol. 2014 Jul-Aug;64(4):292-8. doi: 10.1016/j.bjan.2013.06.009. Epub 2014 Jun 3. Portuguese.</citation>
    <PMID>25096778</PMID>
  </reference>
  <reference>
    <citation>Delogu G, Antonucci A, Signore M, Marandola M, Tellan G, Ippoliti F. Plasma levels of IL-10 and nitric oxide under two different anaesthesia regimens. Eur J Anaesthesiol. 2005 Jun;22(6):462-6. doi: 10.1017/s0265021505000797.</citation>
    <PMID>15991511</PMID>
  </reference>
  <reference>
    <citation>Turan A, Hesler BD, You J, Saager L, Grady M, Komatsu R, Kurz A, Sessler DI. The association of serum vitamin D concentration with serious complications after noncardiac surgery. Anesth Analg. 2014 Sep;119(3):603-612. doi: 10.1213/ANE.0000000000000096.</citation>
    <PMID>25121616</PMID>
  </reference>
  <reference>
    <citation>Pludowski P, Ducki C, Konstantynowicz J, Jaworski M. Vitamin D status in Poland. Pol Arch Med Wewn. 2016 Aug 9;126(7-8):530-9. doi: 10.20452/pamw.3479. Epub 2016 Aug 9.</citation>
    <PMID>27509842</PMID>
  </reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>May 23, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>February 5, 2022</last_update_submitted>
  <last_update_submitted_qc>February 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Lodz</investigator_affiliation>
    <investigator_full_name>Anna Grzegory</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>dexamethasone</keyword>
  <keyword>hypocalcaemia</keyword>
  <keyword>hypocalcemic symptoms</keyword>
  <keyword>postoperative complications</keyword>
  <keyword>vitamin D deficiency</keyword>
  <keyword>cytokines</keyword>
  <keyword>postoperative pain</keyword>
  <keyword>postoperative nausea</keyword>
  <keyword>postoperative vomiting</keyword>
  <keyword>hoarseness</keyword>
  <keyword>acute phase proteins</keyword>
  <keyword>hypoparathyroidism</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hoarseness</mesh_term>
    <mesh_term>Dysphonia</mesh_term>
    <mesh_term>Vitamin D Deficiency</mesh_term>
    <mesh_term>Hypocalcemia</mesh_term>
    <mesh_term>Hypoparathyroidism</mesh_term>
    <mesh_term>Pain, Postoperative</mesh_term>
    <mesh_term>Nausea</mesh_term>
    <mesh_term>Postoperative Complications</mesh_term>
    <mesh_term>Postoperative Nausea and Vomiting</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>BB 1101</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All IPD will be included in planned publication.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>starting 6 months after publication</ipd_time_frame>
    <ipd_access_criteria>planned publication, journal website</ipd_access_criteria>
  </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/NCT04412694
org study id: MULODZ nr RNN/133/20/KE
nct id: NCT04412694
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Glucocorticoids are well known for their analgesic, anti-inflammatory, immunomodulatory and
      anti-emetic effects. Recovery time after thyroid surgery may depend on several factors, such
      as postoperative pain, nausea and vomiting, postoperative sore throat, voice disorders and
      symptomatic hypocalcaemia (low serum calcium level). However, there is little information in
      the literature about the preventive use of glucocorticosteroids in patients undergoing
      thyroid surgery. The aim of the study is to evaluate the clinical impact of preoperative oral
      dexamethasone supplementation on the surgical outcome in patients with multinodular goiter
      undergoing total thyroidectomy. Patients will be assigned to the supplementation group and
      the placebo group. In the supplementation group 8mg of dexamethasone will be administered
      orally one hour before surgery. In the postoperative period, the frequency and intensity of
      pain, nausea, vomiting, sore throat and hoarseness will be assessed. The incidence of
      symptoms of hypocalcaemia will also be evaluted. Preoperative and postoperative levels of
      vitamin D, cytokines, acute phase proteins and substances related to calcium metabolism will
      be measured in the blood. Cytokines levels in drainage fluid will also be assessed. The main
      hypothesis of the study is that in patients with supplementation postoperative discomfort and
      decrease in serum calcium and parathormone level and hypocalcemic symptoms will be less
      severe and the levels of proinflammatory substances will be decreased.
Recovery time after thyroid surgery may depend on several factors, such as postoperative
      pain, nausea and vomiting, postoperative sore throat, phonation disorders associated with
      recurrent laryngeal nerve palsy, and symptomatic postoperative hypocalcaemia associated with
      postoperative hypoparathyroidism.

      Glucocorticoids are well known for their analgesic, anti-inflammatory, immunomodulatory and
      anti-emetic effects. However, there is little information in the literature on the
      prophylactic use of glucocorticosteroids in patients undergoing thyroid surgery. In some
      previous studies, preoperative intravenous dexamethasone supplementation was associated with
      a reduced incidence of postoperative laryngeal nerve palsy, postoperative hypoparathyroidism,
      and with less severe postoperative pain, postoperative sore throat, nausea and vomiting.
      Patients receiving supplementation also had decreased levels of inflammatory biochemical
      parameters and proinflammatory cytokines.

      Vitamin D deficiency is widespread in Poland. Vitamin D status has an impact on the
      postoperative complications in surgical patients. In previous study serum 25-hydroxyvitamin D
      is also suggested as a negative acute phase reactant, which has implications for acute and
      chronic inflammatory diseases. According to the authors, serum 25-hydroxyvitamin D level is
      an unreliable biomarker of vitamin D status after acute inflammatory insult.

      In the early stages of inflammation, phagocytic cells and endothelium secrete proinflammatory
      cytokines, which include: interleukins: IL-1 α / β, IL-6, IL-8, TNF. The antagonistic group
      is anti-inflammatory cytokines, which include interleukins: IL-4, -5, -10, -13, produced by
      Th2 lymphocytes. These cytokines reduce the amount of interleukins secreted by Th1
      lymphocytes.

      Changes in the levels of proinflammatory and anti-inflammatory cytokines in the postoperative
      period were found in studies related to the assessment of surgical trauma. Pro-inflammatory
      interleukin 1 and interleukin 6 play an important role in many biological processes such as
      inflammation, sepsis and wound healing. Interleukin 6 expression is proportional to the
      extent of the surgical trauma. In turn, interleukin 10 is known as a cytokine that inhibits
      cytokine synthesis. Is one of the strongest immunosuppressive agents.

      The aim of my study is to evaluate the impact of preoperative oral dexamethasone
      supplementation on the biochemical parameters and results of surgical treatment in patients
      with nontoxic multinodular goiter undergoing total thyroidectomy.

      Patients admitted to the Department of General and Oncological Surgery, Medical University of
      Lodz with preoperative diagnosis of nontoxic multinodular goitre undergoing total
      thyroidectomy will be inculded to the study.

      After obtaining written informed consent from all participants during a preoperative visit,
      they will be randomized to the supplementation group and the placebo group. The study will be
      a prospective, placebo-controlled and double-blind (for patient and surgeon) research.

      Intervention: In the supplementation group a single dose of 8mg of dexamethasone will be
      given orally one hour before surgery (Dexamethasone Krka tablets (8mg), Warsaw, Poland). In
      the placebo group patients will receive a single tablet of sweetener one hour before
      operation (Clio tablets, sweetener with a dispenser, Instantina GES, Vienna, Austria).

      Preoperatively in the group of all enrolled patients (in the supplementation group and in the
      placebo group) following tests will be measured in serum: blood count, calcium, inorganic
      phosphates, albumin, alkaline phosphatase, C reactive protein, procalcitonin,
      25-hydroxyvitamin D, fibrinogen, parathormone, magnesium, interleukin 1β, interleukin 6,
      interleukin 10, thyroid stimulating hormone, free thyroxine, free triiodothyronine.

      Total thyroidectomies with routine identification of the recurrent laryngeal nerves and
      parathyroid glands via a transverse cervicotomy under general anaesthesia will be performed
      by 3 experienced surgeons.

      During the total thyroidectomy the number of parathyroid glands found intraoperatively will
      be registered.

      At 6 hour after surgery in the group of all enrolled patients following tests will be
      measured in serum: blood count, calcium, inorganic phosphates, albumin, alkaline phosphatase,
      C reactive protein, procalcitonin, 25-hydroxyvitamin D, fibrinogen, parathormone, magnesium.
      In addiction, at 6 hour after surgery the incidence and intensity of symptomatic
      hypocalcaemia, postoperative pain (according to VAS scale), postoperative nausea and
      vomiting, postoperative sore throat and hoarseness will be evaluated.

      At 24 hour after surgery in the group of all enrolled patients following tests will be
      measured in serum: blood count, calcium, inorganic phosphates, albumin, alkaline phosphatase,
      C reactive protein, procalcitonin, 25-hydroxyvitamin D, fibrinogen, parathormone, magnesium,
      interleukin 1β, interleukin 6, interleukin 10. Additionally, the level of interleukin 1β,
      interleukin 6 and interleukin 10 will be evaluated in drainage fluid. In addiction, at 24
      hour after surgery the incidence and intensity of symptomatic hypocalcaemia, postoperative
      pain (according to Visual Analogue Scale - VAS scale), postoperative nausea and vomiting,
      postoperative sore throat and hoarseness will be evaluated.

      The laboratory parameters will be determined by electrochemiluminescence on the Cobas E411
      analyzer and spectrophotometric method on the AU680, Beckman Coulter analyzer.
      25-hydroxyvitamin D levels will be measured using the chemiluminescent microparticle
      immunoassay (CMIA) (Architect 25-OHD). Interleukins levels will be determined by enzyme
      immunoassay method (EIA) (DGR Medtek) on ElizaMat 2 X analyzer.

      Hypocalcemic symptoms will be categorized as mild (a tingling sensation and numbness of the
      hands or feet and perioral numbness) or severe (a positive Chvostek sign, Trousseau sign,
      tetany, and carpopedal spasms).

      Postoperative hypocalcaemia will be defined as corrected calcium levels <2.0 mmol/l, even if
      recorded in one measurement only.

      In both groups participants who will develop postoperative hypoparathyroidism (parathormone
      level <1.6 pmol/l at 6 or 24 hour after surgery) or symptomatic hypocalcaemia during
      hospitalisation will be treated with oral calcium (3 g/d - taken 1 g every 8 hours) and
      vitamin D derivatives (1 ug/d alfacalcidol taken once).

      Intravenous calcium gluconate will be administered if symptoms persist despite oral
      supplementation.

      Patients with symptomatic hypocalcaemia will receive supplementation until the symptoms
      subside. The treatment will be extended to 6 weeks in patients with hypoparathyroidism on the
      day of discharge.

      The data will be statistically analysed. The main hypothesis of the study is that in patients
      with supplementation postoperative discomfort and decrease in serum calcium and parathormone
      level and hypocalcemic symptoms will be less severe and the levels of proinflammatory
      substances will be decreased. Vitamin D deficiency is probably common in operated patients
      and postoperative 25-hydroxyvitamin D levels are lower than those measured preoperatively.

      The use of oral dexamethasone might be an effective strategy of prevention of complications
      after total thyroidectomy.

      To the best of our knowledge, this is a pioneering study assessing the usefulness of
      preventive oral dexamethasone supplementation before total thyroidectomy in homogeneous group
      of patients with nontoxic multinodular goiter undergoing total thyroidectomy.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients will be randomly assigned (coin toss) to the supplementation group (preoperative oral supplementation of dexamethasone (8mg in one dose) taken one hour before surgery) and to the placebo group (preoperative oral supplementation of sweetener taken one hour before surgery).
primary purpose: Prevention
masking: Double (Participant, Care Provider)
measure: Postoperative hypocalcaemia
time frame: preoperatively and at 6 and 24 hour after surgery
description: To evaluate the incidence of laboratory hypocalcaemia (corrected calcium serum level <2.0 mmol/l), the change in calcium levels and symptomatic hypocalcaemia in the postoperative period in the supplementation group and in the placebo group.
measure: Postoperative hypoparathyroidism
time frame: preoperatively and at 6 and 24 hour after surgery
description: To evaluate the incidence of hypoparathyroidism (parathormone serum level <1.6 pmol/l) and the change in parathormone levels in the postoperative period in the supplementation group and in the placebo group.
measure: Postoperative pain
time frame: at 6 and 24 hour after surgery
description: To evaluate the intensity of postoperative pain according to Visual Analogue Scale (VAS scale) in the postoperative period in the supplementation group and in the placebo group. Minimum value is 0 (no pain) and maximum value is 10 (the worst possible pain). Higher scores mean a worse outcome.
measure: Postoperative nausea on a verbal rating scale
time frame: at 6 and 24 hour after surgery
description: To evaluate the incidence and the intensity of postoperative nausea in the postoperative period in the supplementation group and in the placebo group. The intensity of nausea will be rated on a verbal rating scale based on verbal responses of the patient to questions: 0 - no nausea; 1 - mild nausea (1 episode of nausea); 2 - moderate nausea (2 or 3 episodes of nausea ); and 3 - severe nausea (>3 episodes of nausea ). Higher scores mean a worse outcome.
measure: Postoperative vomiting on a verbal rating scale
time frame: at 6 and 24 hour after surgery
description: To evaluate the incidence and the intensity of postoperative vomiting in the postoperative period in the supplementation group and in the placebo group.The intensity of vomiting will be rated on a verbal rating scale based on verbal responses of the patient to questions: 0 - no episodes of vomiting; 1 - mild vomiting (1 episode of vomiting); 2 - moderate vomiting (2 or 3 episodes of vomiting); and 3 - severe vomiting (>3 episodes of vomiting).Higher scores mean a worse outcome.
measure: Postoperative sore throat on a verbal rating scale
time frame: at 6 and 24 hour after surgery
description: To evaluate the incidence and the intensity of postoperative sore throat in the postoperative period in the supplementation group and in the placebo group. Postoperative sore throat will be defined as discomfort at larynx or pharynx at rest and during swallowing after surgery. The intensity of sore throat will be rated on a verbal rating scale based on verbal responses of the patient to questions: 0 - none; 1 - mild sore throat (less severe than with a cold); 2 - moderate sore throat (similar with a cold); and 3 - severe sore throat (more severe than with a cold). Higher scores mean a worse outcome.
measure: Postoperative hoarseness on a verbal rating scale
time frame: at 6 and 24 hour after surgery
description: To evaluate the incidence and the intensity of postoperative hoarseness in the postoperative period in the supplementation group and in the placebo group. The intensity of hoarseness will be rated on a verbal rating scale based on verbal responses of the patient to questions: 0 - none; 1 - mild hoarseness (noticed by the patient only); 2 - severe hoarseness (obvious to observer); 3 - aphonia (silence of voice). Higher scores mean a worse outcome.
measure: Cytokines in serum
time frame: preoperatively and at 6 and 24 hour after surgery
description: To evaluate the serum levels of cytokines such as interleukin 1β, interleukin 6, interleukin 10 and the change in cytokines levels in the postoperative period in the supplementation group and in the placebo group.
measure: Cytokines in drain fluid
time frame: at 24 hour after surgery
description: To evaluate the levels of cytokines such as interleukin 1β, interleukin 6, interleukin 10 in the drain fluid in the postoperative period in the supplementation group and in the placebo group.
measure: Calcium phosphate homeostasis
time frame: preoperatively and at 6 and 24 hour after surgery
description: To evaluate the serum levels of alkaline phosphatase,inorganic phosphates and magnesium and the change in their levels in the postoperative period in the supplementation group and in the placebo group.
measure: Vitamin D
time frame: preoperatively and at 6 and 24 hour after surgery
description: To evaluate the levels of 25-hydroxyvitamin D in the preoperative and postoperative period and the change in its levels in the supplementation group and in the placebo group. To evaluate the incidence of vitamin D deficiency in the group of operated patients.
measure: Acute phase proteins
time frame: preoperatively and at 6 and 24 hour after surgery
description: To evaluate the serum levels of albumin, C reactive protein, procalcitonin and fibrinogen and the change in their levels in the postoperative period in the supplementation group and in the placebo group.
arm group label: supplementation group
arm group type: Experimental
description: Patients will receive preoperative oral supplementation of 8mg of dexamethasone (Dexamethasone Krka tablets (8mg), Warsaw, Poland) in a single dose taken once one hour before surgery. At 6 and 24 hour after surgery, clinical and laboratory parameters will be measured and evaluated.
arm group label: placebo group
arm group type: Placebo Comparator
description: Patients will receive preoperative oral supplementation of sweetener (Clio tablets, sweetener with a dispenser, Instantina GES, Vienna, Austria) taken once in a single dose one hour before surgery. At 6 and 24 hour after surgery, clinical and laboratory parameters will be measured and evaluated.
intervention type: Drug
intervention name: Dexamethasone oral tablet 8mg (Dexamethasone Krka tablets(8mg), Warsaw, Poland).
description: Preoperative oral dexamathasone supplementation in a single dose of 8mg.
arm group label: supplementation group
other name: Supplementation
intervention type: Drug
intervention name: Placebo oral sweetener (Clio tablets, sweetener with a dispenser, Instantina GES, Vienna, Austria).
description: Preoperative oral supplementation of sweetener in a single dose.
arm group label: placebo group
other name: Placebo
intervention type: Diagnostic Test
intervention name: Preoparative blood laboratory tests
description: Preoperative parameters such as blood count, calcium, inorganic phosphates, albumin, alkaline phosphatase, C reactive protein, procalcitonin, 25-hydroxyvitamin D, fibrinogen, parathormone, magnesium, interleukin 1β, interleukin 6, interleukin 10, thyroid stimulating hormone, free thyroxine, free triiodothyronin will be measured in serum.
arm group label: placebo group
arm group label: supplementation group
other name: preoperative blood test
intervention type: Diagnostic Test
intervention name: Postoperative laboratory blood tests at 6 hour
description: At 6 hour after surgery such parameters as blood count, calcium, inorganic phosphates, albumin, alkaline phosphatase, C reactive protein, procalcitonin, 25-hydroxyvitamin D, fibrinogen, parathormone, magnesium will be measured in serum.
arm group label: placebo group
arm group label: supplementation group
other name: blood tests 6 hour
intervention type: Diagnostic Test
intervention name: Postoperative laboratory blood tests at 24 hour
description: At 24 hour after surgery such parameters as blood count, calcium, inorganic phosphates, albumin, alkaline phosphatase, C reactive protein, procalcitonin, 25-hydroxyvitamin D, fibrinogen, parathormone, magnesium, interleukin 1β, interleukin 6, interleukin 10 will be measured in serum.
arm group label: placebo group
arm group label: supplementation group
other name: blood tests 24 hour
intervention type: Diagnostic Test
intervention name: Postoperative laboratory drainage fluid tests at 24 hour
description: At 24 hour after surgery such parameters as interleukin 1β, interleukin 6, interleukin 10 will be measured in drainage fluid.
arm group label: placebo group
arm group label: supplementation group
other name: drainage fluid tests 24 hour
intervention type: Procedure
intervention name: Total thyroidectomy
description: Patients will undergo total thyroidectomy under general anesthesia.
arm group label: placebo group
arm group label: supplementation group
other name: thyroidectomy
intervention type: Other
intervention name: Symptomatic hypocalcaemia at 6 hour
description: At 6 hour after surgery patients will be assessed for signs of hypocalcaemia.
arm group label: placebo group
arm group label: supplementation group
other name: symptoms 6 hour
intervention type: Other
intervention name: Symptomatic hypocalcaemia at 24 hour
description: At 24 hour after surgery patients will be assessed for signs of hypocalcaemia.
arm group label: placebo group
arm group label: supplementation group
other name: symptoms 24 hour
intervention type: Other
intervention name: Postoperative pain at 6 hour
description: At 6 hour after surgery the incidence and intensity of postoperative pain will be evaluated according to Visual Analogue Scale (VAS).
arm group label: placebo group
arm group label: supplementation group
other name: pain 6 hour
intervention type: Other
intervention name: Postoperative pain at 24 hour
description: At 24 hour after surgery the incidence and intensity of postoperative pain will be evaluated according to Visual Analogue Scale (VAS).
arm group label: placebo group
arm group label: supplementation group
other name: pain 24 hour
intervention type: Other
intervention name: Postoperative nausea and vomiting at 6 hour
description: At 6 hour after surgery the incidence and intensity of postoperative nausea and vomiting will be evaluated.
arm group label: placebo group
arm group label: supplementation group
other name: nausea 6 hour
intervention type: Other
intervention name: Postoperative nausea and vomiting at 24 hour
description: At 24 hour after surgery the incidence and intensity of postoperative nausea and vomiting will be evaluated.
arm group label: placebo group
arm group label: supplementation group
other name: nausea 24 hour
intervention type: Other
intervention name: Postoperative sore throat and hoarseness at 6 hour
description: At 6 hour after surgery the incidence and intensity of postoperative sore throat and hoarseness will be evaluated.
arm group label: placebo group
arm group label: supplementation group
other name: hoarseness 6 hour
intervention type: Other
intervention name: Postoperative sore throat and hoarseness at 24 hour
description: At 24 hour after surgery the incidence and intensity of postoperative sore throat and hoarseness will be evaluated.
arm group label: placebo group
other name: hoarseness 24 hour
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Anna Grzegory, MD
role: Principal Investigator
affiliation: Medical University of Lodz, Poland
last name: Anna Grzegory, MD
phone: 695720008
phone ext: +48
email: an.grzegory@gmail.com
facility: 
status: Recruiting
contact: 
country: Poland
citation: Schietroma M, Cecilia EM, Carlei F, Sista F, De Santis G, Lancione L, Amicucci G. Dexamethasone for the prevention of recurrent laryngeal nerve palsy and other complications after thyroid surgery: a randomized double-blind placebo-controlled trial. JAMA Otolaryngol Head Neck Surg. 2013 May;139(5):471-8. doi: 10.1001/jamaoto.2013.2821.
PMID: 23681030
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responsible party type: Principal Investigator
investigator affiliation: Medical University of Lodz
investigator full name: Anna Grzegory
investigator title: Principal Investigator
mesh term: Hoarseness
mesh term: Dysphonia
mesh term: Vitamin D Deficiency
mesh term: Hypocalcemia
mesh term: Hypoparathyroidism
mesh term: Pain, Postoperative
mesh term: Nausea
mesh term: Postoperative Complications
mesh term: Postoperative Nausea and Vomiting
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: BB 1101
sharing ipd: Yes
ipd description: All IPD will be included in planned publication.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: starting 6 months after publication
ipd access criteria: planned publication, journal website