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.

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.

Hypocalcemia

Vitamin D Deficiency

Postoperative Complications

Postoperative Nausea

Postoperative Pain

Voice Hoarseness

Hypoparathyroidism Postprocedural

Preoperative oral dexamathasone supplementation in a single dose of 8mg.

Dexamethasone oral tablet 8mg (Dexamethasone Krka tablets(8mg), Warsaw, Poland).

Preoperative oral supplementation of sweetener in a single dose.

Placebo oral sweetener (Clio tablets, sweetener with a dispenser, Instantina GES, Vienna, Austria).

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.

Preoparative blood laboratory tests

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.

Postoperative laboratory blood tests at 6 hour

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.

Postoperative laboratory blood tests at 24 hour

At 24 hour after surgery such parameters as interleukin 1β, interleukin 6, interleukin 10 will be measured in drainage fluid.

Postoperative laboratory drainage fluid tests at 24 hour

Patients will undergo total thyroidectomy under general anesthesia.

Total thyroidectomy

At 6 hour after surgery patients will be assessed for signs of hypocalcaemia.

Symptomatic hypocalcaemia at 6 hour

At 24 hour after surgery patients will be assessed for signs of hypocalcaemia.

Symptomatic hypocalcaemia at 24 hour

At 6 hour after surgery the incidence and intensity of postoperative pain will be evaluated according to Visual Analogue Scale (VAS).

Postoperative pain at 6 hour

At 24 hour after surgery the incidence and intensity of postoperative pain will be evaluated according to Visual Analogue Scale (VAS).

Postoperative pain at 24 hour

At 6 hour after surgery the incidence and intensity of postoperative nausea and vomiting will be evaluated.

Postoperative nausea and vomiting at 6 hour

At 24 hour after surgery the incidence and intensity of postoperative nausea and vomiting will be evaluated.

Postoperative nausea and vomiting at 24 hour

At 6 hour after surgery the incidence and intensity of postoperative sore throat and hoarseness will be evaluated.

Postoperative sore throat and hoarseness at 6 hour

At 24 hour after surgery the incidence and intensity of postoperative sore throat and hoarseness will be evaluated.

Postoperative sore throat and hoarseness at 24 hour

The Effect of Preoperative Oral Dexamethasone Supplementation on the Outcome of Thyroidectomised Patients.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

All IPD will be included in planned publication.

Anna Grzegory

Principal Investigator

Medical Universtity of Lodz

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).

The intervention is K1-70 intramuscular or K1-70 intravenous. This is a single, ascending, intramuscular or intravenous dose, sequential group study.

Graves' Disease

Each subject will receive one dose of K1-70 by IM injection or one dose of K1-70 by IV infusion on the morning of Day 1.

K1-70 intramuscular or K1-70 intravenous

Royal Liverpool University Hospital Clinical Research Unit

Medicines Evaluation Unit

K1-70 - A Study in Subjects With Graves' Disease

K1-70 - A Phase I, Single Ascending Intramuscular Dose or Single Ascending Intravenous Dose, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study in Subjects With Graves' Disease

Safety and tolerability testing consists of vital signs, ECG, blood samples for haematology, coagulation, clinical biochemistry and hormone panel, urine samples for urinalysis, eye examinations, physical examinations and examination of injection or infusion site. All clinically significant results and the number of treatment related adverse events will be reported.

The terminal elimination rate constant will be calculated and reported

The terminal elimination half life will be calculated and reported

Time of the maximum observed plasma concentration will be calculated and reported

Maximum observed plasma concentration will be calculated and reported

Area under the plasma concentration time curve to the last quantified concentration will be calculated and reported

Area under the plasma concentration time curve from time zero to infinity will be calculated and reported

Percentage of area under the plasma concentration time curve that is extrapolated will be calculated and reported

The level of antidrug antibodies present in the patient serum will be measured over time and reported.

TSH levels will be measured and reported over time.

Free T3 levels will be measured and reported over time.

Free T4 levels will be measured and reported over time.

TSH levels will be reported against baseline TRAb over time.

Free T3 levels will be reported against baseline TRAb over time.

Free T4 levels will be reported against baseline TRAb over time.

All clinically significant results and the number of treatment related adverse events will be reported.

goiter/misselijkheid

The Effect of Preoperative Oral Dexamethasone Supplementation on the Outcome of Thyroidectomised Patients.

K1-70 - A Study in Subjects With Graves' Disease

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