Intraoperative Parathyroid Hormone Monitoring to Guide Surgery in Renal hyperparathyroIdism (PEREGRINE)

McMaster University

Status: Not yet enrolling

Conditions: Tertiary Hyperparathyroidism; Secondary Hyperparathyroidism

Treatments: Procedure: Intraoperative parathyroid hormone (IOPTH) monitoring

Study type: Interventional

Funder types: Other

Identifiers

NCT06542315

151132

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18 years of age or older
• Candidate for subtotal parathyroidectomy or total thyroidectomy with or without autotransplantation
• Tertiary hyperparathyroidism and/or recurrent hyperparathyroidism OR secondary hyperparathyroidism diagnosed with any stage of chronic kidney disease

Exclusion criteria

• Undergoing parathyroidectomy for primary hyperparathyroidism
• Pregnant or breastfeeding women
• Undergoing revision parathyroidectomy
• Undergoing minimally invasive or video-assisted parathyroidectomy
• Unable to provide written consent to be participant in study
• Unable to complete study follow-up visits

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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60 participants in 5 patient groups

No IOPTH monitoring arm

No Intervention group

Description:

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.

10 minute arm

Experimental group

Description:

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.

Treatment:

Procedure: Intraoperative parathyroid hormone (IOPTH) monitoring

15 minute arm

Experimental group

Description:

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.

Treatment:

Procedure: Intraoperative parathyroid hormone (IOPTH) monitoring

20 minute arm

Experimental group

Description:

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.

Treatment:

Procedure: Intraoperative parathyroid hormone (IOPTH) monitoring

25 minute arm

Experimental group

Description:

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.

Treatment:

Procedure: Intraoperative parathyroid hormone (IOPTH) monitoring