Intraoperative Parathyroid Hormone Monitoring to Guide Surgery in Renal hyperparathyroIdism

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.

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).

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.

Defined as completion of all questionnaires and study bloodwork from randomization to final study follow-up.

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.

Any changes to the surgical plan will be documented by surgeons in a postoperative de-brief form.

The length of the surgery from skin incision to skin closure, as measured in minutes

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.

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).

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.

The IOPTH change (as a percent) between time points will be described.

Number of emergency room visits and hospital readmissions due to surgical complications.

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.

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.

Number of patients who have renal transplantation who experienced renal graft failure and/or complication during the study period.

These will be measured by calculating the number of patients who develop hypoparathyroidism and/or hypocalcemia following surgery.

The types of surgical complications will be documented.

This will be collected during the study period. It will include operative and inpatient/outpatient costs for each randomized patient.

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.