An interventional study of Intraoperative parathyroid hormone (IOPTH) monitoring in Secondary Hyperparathyroidism and Tertiary Hyperparathyroidism, sponsored by McMaster University. Not yet recruiting at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-08-07.
Sponsored by McMaster University · Not applicable, Interventional, and Other
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.
188 studies on the registry are indexed under Hyperparathyroidism, Secondary; 15 are open to participants now.
This study's planned enrollment of 60 is close to the median of 62 across 146 interventional studies indexed under Hyperparathyroidism, Secondary.
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Of its 7 completed or terminated interventional studies of FDA-regulated products, 3 (43%) have results posted.
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Exclusion Criteria:
Surgery for patients randomized to this arm will not require guidance with any IOPTH monitoring. These will be allowed to use frozen section analysis, if deemed appropriate by the surgeon.
Surgery for patients randomized to this arm will need to use IOPTH monitoring. Surgeons in this arm will decide to end surgery or perform surgical re-exploration if the IOPTH level at 10 minutes following ligation of all hyperfunctioning parathyroid tissue is \>=50% from the highest pre-incision or pre-excision baseline IOPTH level.
Procedure: Intraoperative parathyroid hormone (IOPTH) monitoring
Surgery for patients randomized to this arm will need to use IOPTH monitoring. Surgeons in this arm will decide to end surgery or perform surgical re-exploration if the IOPTH level at 15 minutes following ligation of all hyperfunctioning parathyroid tissue is \>=50% from the highest pre-incision or pre-excision baseline IOPTH level.
Procedure: Intraoperative parathyroid hormone (IOPTH) monitoring
Surgery for patients randomized to this arm will need to use IOPTH monitoring. Surgeons in this arm will decide to end surgery or perform surgical re-exploration if the IOPTH level at 20 minutes following ligation of all hyperfunctioning parathyroid tissue is \>=50% from the highest pre-incision or pre-excision baseline IOPTH level.
Procedure: Intraoperative parathyroid hormone (IOPTH) monitoring
Surgery for patients randomized to this arm will need to use IOPTH monitoring. Surgeons in this arm will decide to end surgery or perform surgical re-exploration if the IOPTH level at 25 minutes following ligation of all hyperfunctioning parathyroid tissue is \>=50% from the highest pre-incision or pre-excision baseline IOPTH level.
Procedure: Intraoperative parathyroid hormone (IOPTH) monitoring
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.
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
Surgeon-dictated changes to intraoperative plan
Any changes to the surgical plan will be documented by surgeons in a postoperative de-brief form.
Time frame: From enrollment to the end the trial at 6 months
Operating time
The length of the surgery from skin incision to skin closure, as measured in minutes
Time frame: From enrollment to the end the trial at 6 months
Revision surgery rate and indication for revision surgery
Number of patients who either undergo or are consented and scheduled to undergo revision parathyroidectomy within 6 months of randomization. This will be measured as a dichotomous outcome. We will also evaluate the surgical indication for revision surgery. This will be measured as a categorical outcome.
Time frame: From enrollment to the end the trial at 6 months
Chronic kidney disease progression, cardiovascular death, or renal death (composite outcome)
Number of patients who meet the criteria of this composite outcome (sustained decline in eGFR of at least 50%, end-stage kidney disease, or kidney-related or cardiovascular death).
Time frame: From enrollment to the end the trial at 6 months
Recurrent and/or persistent hyperparathyroidism rates
Number of people who continue to have pathologically elevated PTH levels within 3 months of randomization. This will be measured with reference to the defined PTH reference threshold at each participating institution. This will be measured immediately after surgery and at one month and six months from randomization. We will also measure the number of patients who have laboratory hypercalcemia as defined by bloodwork immediately after surgery and at one month and six months from randomization.
Time frame: From enrollment to the end the trial at 6 months
IOPTH kinetics in secondary and tertiary hyperparathyroidism
The IOPTH change (as a percent) between time points will be described.
Time frame: From enrollment to the end the trial at 6 months
Emergency room visits and hospital readmission rates
Number of emergency room visits and hospital readmissions due to surgical complications.
Time frame: From enrollment to the end the trial at 6 months
Length of hospital stay
Number of days admitted to hospital from the date of surgery to the day of hospital discharge. We will also measure the length of hospital stay for any readmissions from hospital admission to discharge.
Time frame: From enrollment to the end the trial at 6 months
Health-related quality of life
These will be measured using the SF-36 tool and kidney disease quality of life (KDQOL)-36 tool prior to randomization (baseline), and at one month and three months from surgery. The SF-36 is a validated self-reported patient-centred outcome measure (PROM) measured via eight domains on a 0-100 scale with lower scores indicating worse disability. The KDQOL-36 is a validated self-reported PROM scored from 0-100 with higher scores indicating better quality of life.
Time frame: From enrollment to 3 months
Renal graft failure and renal graft complication rates
Number of patients who have renal transplantation who experienced renal graft failure and/or complication during the study period.
Time frame: From enrollment to the end the trial at 6 months
Rates of hypoparathyroidism and hypocalcemia
These will be measured by calculating the number of patients who develop hypoparathyroidism and/or hypocalcemia following surgery.
Time frame: From enrollment to the end the trial at 6 months
Surgery-specific complication rates
The types of surgical complications will be documented.
Time frame: From enrollment to the end the trial at 6 months
Fully powered trial costs
This will be collected during the study period. It will include operative and inpatient/outpatient costs for each randomized patient.
Time frame: From enrollment to the end the trial at 6 months
Cognitive function
These will be measured using the Hospital Anxiety and Depression Scale (HADS) and MoCA prior to randomization (baseline), and at one month and three months postoperatively. In the HADS, higher scores indicate worse anxiety and depression scores with scores ranging from 0-21. In the MoCA, lower scores indicate worse cognitive function with scores ranging from 0-30.
Time frame: From enrollment to 3 months
Plan to share: Undecided — This will need to be further discussed with all trial team members prior to making final decision.
Start is estimated for Oct 2024; primary completion for Apr 2026, 18 months later.
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Hyperparathyroidism, Secondary →