The goal of this pilot clinical is to determine the feasibility of a fully powered clinical trial to determine the effectiveness of intraoperative parathyroid hormone (IOPTH) criteria in guiding surgery for secondary and tertiary hyperparathyroidism. The main question it aims to answer is: Is a fully powered trial investigating the role for IOPTH criteria in secondary and tertiary hyperparathyroidism feasible? The comparison group is surgery not guided by IOPTH. Participants will be randomized to undergo parathyroid surgery with one of four IOPTH criteria or a control arm that does not use IOPTH. All recruited patients are asked to complete quality of life and cognitive questionnaires, in addition to bloodwork during the study period.
Chronic kidney disease (CKD) is increasing in prevalence globally alongside rising rates of obesity and metabolic syndromes. The rates of secondary and tertiary hyperparathyroidism are expected to rise alongside the increasing prevalence of CKD. Secondary hyperparathyroidism is diagnosed in up to 80% of patients with long-standing CKD on hemodialysis and is associated worse renal and cardiovascular outcomes and quality of life. Up to 55% of patients are non-compliant with, or refractory to, medical treatment and therefore require definitive surgery. Up to 22% of patients who undergo renal transplantation also develop tertiary hyperparathyroidism, which is associated with worse patient morbidity and renal graft outcomes. Surgery to extirpate abnormal parathyroid tissue in both diagnoses is technically challenging with surgical failure rates as high as 30%. Intraoperative parathyroid hormone (IOPTH) monitoring, which is a surgical adjunct that uses the short half-life of PTH to guide parathyroid surgery, is standard-of-care in primary hyperparathyroidism. There is no consensus nor standardization in the use of IOPTH monitoring in secondary and tertiary hyperparathyroidism. The investigators propose a multi-centre, multi-arm randomized trial to identify the most effective IOPTH monitoring criteria in improving surgical outcomes in secondary and tertiary hyperparathyroidism. To evaluate the feasibility of a fully powered trial, the investigators will conduct a randomized and blinded multi-centre, multi-arm pilot trial. The investigators plan on evaluating five allocation arms that use four IOPTH monitoring criteria (i.e., 10 minutes, 15 minutes, 20 minutes, and 25 minutes) against a control arm of not using IOPTH monitoring. The primary feasibility outcome is randomization rate. The investigators will aim for a targeted randomization rate of 70% (95% CI: 55%-82%). Secondary feasibility outcomes include group cross-over rate, blinding effectiveness, patient compliance, and pilot trial costs. The primary efficacy outcome is recurrent hyperparathyroidism, which is evaluated at six months. Secondary efficacy outcomes will include operating room time, renal graft outcomes, renal function, cardiovascular outcomes, hospital admission and rate of re-admission, quality of life, cognitive performance. Inclusion criteria will include any adult patients (\>= 18 years old) diagnosed with secondary or tertiary hyperparathyroidism who are candidates for parathyroid surgery. The investigators plan to recruit 60 patients (12 per arm) to evaluate a randomization goal of 70% (95% CI: 55%-82%) while accounting for a 20% attrition rate. The investigators will perform descriptive analyses with ITT principles to evaluate feasibility and use these findings to evaluate the practicality of a fully powered trial. The investigators will perform descriptive analyses for all outcomes with 95% confidence intervals. The investigators will use the stop light model for determining whether a final trial is feasible, whereby a randomization rate equal to or greater than 70% will suggest that such a trial is feasible. The results of a fully powered trial will standardize and identify the role for IOPTH monitoring in optimizing surgical outcomes for secondary and tertiary hyperparathyroidism.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
TRIPLE
Enrollment
60
Intraoperative parathyroid hormone (IOPTH) monitoring, which is a surgical adjunct that permits PTH bloodwork to be drawn during parathyroid surgery to monitor and guide surgical outcomes.
St Joseph's Hospital
Hamilton, Ontario, Canada
Randomization rate
Defined as the number of patients agreeing to participate in the trial and being randomized to any of the allocation groups, divided by the number of eligible patients. We will review this data every two weeks during the pilot trial. A randomization percentage of 70% or greater will support the feasibility of a fully powered RCT. We will utilize the traffic light system introduced by Avery and colleagues, whereby if randomization of 70% or greater is achieved, we will proceed with fully powered trial. If a randomization rate of 50-69% is achieved, we will consider proceeding with modifications to the fully powered trial. If randomization rate is \<50%, we will not proceed with fully powered trial. We selected this as a primary feasibility outcome because we are sampling from a relatively rare population, and so gathering an accurate estimate of randomization rate will allow us to determine the ideal number of participating sites for the final trial.
Time frame: From enrollment to the end the trial at 6 months
Blinding effectiveness
The Bang Blindness Inventory (BBI) will be administered to patients, outcome assessors, and statisticians at the end of study follow-up and the time of trial completion (for statisticians). The BBI will then be calculated for each of these blinded parties and reported on a scale of -1 (unblinding) to 0 (perfect blinding) to +1 (lack of blinding).
Time frame: From enrollment to the end the trial at 6 months
Surgeon compliance and crossover
Surgeon compliance and crossover: The number of patients who undergo surgery with a different IOPTH monitoring criteria from which they were randomized. All surgeons will complete a postoperative de-brief form that will capture their rationale for changing groups. We will consider any percentage of group crossover to hinder consideration of a fully powered trial and based on the direction and number of groups crossovers. If any crossovers are detected, then we will consider to the number and organization of allocation arms for the fully powered trial.
Time frame: From enrollment to the end the trial at 6 months
Follow-up completion
Defined as completion of all questionnaires and study bloodwork from randomization to final study follow-up.
Time frame: From enrollment to the end the trial at 6 months
Trial costs
We will estimate the study and hospital costs required for this multi-centre initiative for each recruited patient during the study period. This will provide an estimate of the costs for performing the fully powered trial.
Time frame: From enrollment to the end the trial at 6 months
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