| Participants |
Condition: multinodular goitre
Enrolment: estimated 96
Inclusion criteria:
clinical diagnosis of multinodular goitre, judged clinically and by ultrasound at screening to be at least 40 mL, but ≤ 140 mL in size clinically free of thyroid cancer as determined by Fine Needle Aspiration (FNA) of all dominant, or highly suspicious cold nodules in the goitre, and cytology reports as negative for thyroid cancer (Note: results of FNA and cytology reports that were performed within 18 months prior to commencing screening procedures and met these criteria were acceptable for inclusion) principal Investigator believes there is a minimal risk of coexistent thyroid cancer principal Investigator feels the participant's iodine intake or levels will not significantly impact the results of the study (urinary iodine assay at screening and low‐iodine diet were optional and associated data will not be collected for study purposes) baseline serum level of free thyroxine index (FTI) within the normal range, as determined by central lab baseline serum level of thyroid stimulating hormone (TSH) ranges from undetectable to the upper limit of the normal range, as determined by central lab females of child‐bearing potential must be on a stable hormonal contraceptive regimen (i.e. > 6 months continuous use), or use a double barrier method (i.e. condom and foam) through to visit 8 (i.e. the end of the core study) through to visit 8 (6 months) for male participation in the study, it is recommended that his sexual partner(s), who are females of child‐bearing potential, use the above described methods of contraception. negative pregnancy tests for all women of child‐bearing potential prior to participating in the study women aged 50 years and above and considered postmenopausal (defined as > 2 years since last menstrual period) will not need to have a pregnancy test routine blood laboratory values within normal range at screening, as determined by central lab abnormal values considered not clinically significant by the Principal Investigator are acceptable for inclusion electrocardiogram (ECG; 12 lead, 2 minute rhythm strip) within normal limits at screening as determined by a designated study cardiologist or appropriately qualified physician at each site. Excludion ‐ evidence of an old myocardial infarction (MI); ECG findings of occasional premature atrial beats, abnormal PR intervals not associated with supra ventricular tachycardia (SVT) or heart block, right bundle branch block, and heart rates ≤ 100 beats per minute (BPM), and ≥ 50 BPM committed to follow all protocol‐required study procedures, as evidenced by providing written informed consent within 21 days prior to screening period 2.
Exclusion criteria:
history of thyroid cancer previous partial or near total thyroidectomy clinical history, signs or symptoms that make thyroid cancer a higher than usual probability, such as positive immediate family history of thyroid cancer, history of head or neck irradiation, a stone‐hard nodule, or suspicious growth of a nodule in recent months, palpable cervical lymph nodes, or nodes that on ultrasound have features suspicious for metastases (unless ruled out by biopsy or FNA) during the 45 days before administration of MRrhTSH or placebo (i.e. screening periods 1 and 2), use of propylthiouracil, methimazole or thyroxine, vitamins or supplements containing kelp or iodine (taking a multivitamin that does not contain iodine or kelp is acceptable), medications that significantly affect iodine handling, such as high dose corticosteroids, high dose diuretics, or lithium (low or moderate dose diuretic use is acceptable) currently or within the past 60 days used retinoic acid serum calcitonin above the upper limit of normal at screening, as determined by central lab use of amiodarone within the prior 2 years received iodine‐containing contrast agent within the past 3 months inability to complete all required visits conditions in which use of beta‐blockers are medically contraindicated, such as recently active asthma or clinically significant chronic obstructive pulmonary disease currently, or within the past 5 years, have a history of malignancy, other than squamous or basal cell carcinoma of the skin, or carcinoma in situ of the cervix prior MI, even if remote; stroke within 6 months; atrial fibrillation or clinically significant arrhythmia within 6 months (person may have mild hypertension or chronic cardiac illnesses that are well controlled on a medication regimen: blood pressure (BP) less than 140/90 mmHg after resting 5 minutes) concurrent major medical disorder (e.g. documented significant cardiac disease, debilitating cardiopulmonary disease, advanced renal failure, advanced liver disease, advanced pulmonary disease, or advanced cerebral vascular disorder) that may have an impact on the capability of the person to adequately comply with the requirements of this study women who are pregnant or lactating recent history of alcoholism, drug abuse, or other disorder that might affect compliance with the protocol received investigational study medication within 30 days prior to signing informed consent, or intends to participate in another clinical study involving the use of an investigational drug over the course of study participation. taking anticoagulants, except for aspirin at the time of screening, know to be human immunodeficiency virus (HIV) antibody positive or hepatitis B antigen positive (no screening for HIV or hepatitis B should be done in the study). hyperthyroid symptom scale (HSS) ≥ 20 people who have received 131I in the past, and have had a lifetime exposure believed to be >10 mCi (0.37GBq) of 131I history of allergy to thyrogen, sodium carboxymethylcellulose (NaCMC; including prior history of anaphylaxis following topical lidocaine, barium sulfate ingestion, or intra‐articular or parenteral corticosteroid). smallest cross‐sectional area of the trachea (SCAT) discovered on CT to be < 60 mm²
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| Outcomes |
Primary outcome(s): change from baseline to 6, 36 months in goitre size by computer tomography (CT) scan
Secondary outcome(s): change in goitre size from baseline to 6 months in smallest cross sectional area of the trachea, the percentage of participants in each group who attained a goitre volume shrinkage at 6,12, 36 months of 28% or greater, thyroid Quality of Life Questionnaire, thyroid stimulating hormone (TSH), free thyroxine (FT4), total thyroxine (TT4), FT1, free triiodothyronine (FT3), total T3 (TT3), physical exams, vitals, adverse events, respiratory symptoms, tracheal diameter measurements determined by ultrasound, electrocardiogram (ECG), treatment‐emergent hyperthyroidism |
