Cinacalcet Versus Parathyroidectomy in Peritoneal Dialysis Patients (PROCEED)

Comparison of Medical Therapy (Oral Cinacalcet) Versus Surgical Therapy (Total Parathyroidectomy) on Vascular/Valvular Calcification in Chronic Peritoneal Dialysis Patients With Secondary Hyperparathyroidism - A Pilot Randomized Study

This is a pilot, prospective randomized controlled study with the primary objective to evaluate and compare medical treatment of severe SHPT, namely oral cinacalcet versus surgical treatment, that is, parathyroidectomy with forearm autografting, on the progression of coronary artery and valvular calcification and left ventricular mass index in endstage renal disease patients receiving peritoneal dialysis over 12 months. The change in arterial stiffening, left ventricular volume, aortic valve calcium score and bone mineral density, nutritional status and biochemical parameters, quality of life measures will be evaluated as secondary objectives of this study.

Study Overview

• Status: Completed
• Conditions: Vascular Diseases; Secondary Hyperparathyroidism; Kidney Failure
• Intervention / Treatment: Drug: Cinacalcet; Procedure: Surgical total parathyroidectomy with forearm autografting

Detailed Description

Patients with severe secondary hyperparathyroidism (SHPT) are frequently complicated with vascular calcification. There is some suggestion that subtotal parathyroidectomy may reduce or stabilize vascular calcium scores in dialysis patients. Experimental data suggests that SHPT plays an important role in mediating uraemic arterial disease and that parathyroidectomy largely prevented the development of calcification. Cinacalcet has emerged as a novel therapy for the treatment of SHPT and has been shown to reduce the need for surgical parathyroidectomy. However, their effects on vascular, cardiac, bone and nutrition status have not been evaluated and compared with parathyroidectomy.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 4

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong, 0000
    • Queen Mary Hospital and Tung Wah Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ESRD patients on long-term peritoneal dialysis treatment, with elevated intact parathyroid hormone (iPTH) levels > 800pg/mL.
2. Patients with parathyroid nodular or diffuse hyperplasia demonstrated on ultrasound imaging or radioisotope scan.
3. Patients with age between 18 - 75 years.

Exclusion Criteria:

1. Patients with background valvular heart disease
2. Patients who are unfit for general anaesthesia
3. Patients with acute myocardial infarction within recent two months
4. Patients with poor general condition
5. Patients with plans for living related kidney transplant within 1 year
6. Patients with previous history of parathyroidectomy
7. Patients with underlying malignancy
8. Patients with hepatic dysfunction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cinacalcet treatment; Oral Cinacalcet treatment arm, 25mg daily to be administered and gradually step up as required to control iPTH between 2 - 9 times lab reference range, Maximum dose to be given is 100mg daily	Drug: Cinacalcet; oral cinacalcet 25mg once daily as a start and up titrated by 25mg daily according to response in lowering PTH and maximum oral dose allowed is 100mg daily; Other Names: Regpara
ACTIVE_COMPARATOR: Surgical total parathyroidectomy; Surgical total parathyroidectomy with forearm autografting will be performed for patients randomized to this arm.	Procedure: Surgical total parathyroidectomy with forearm autografting; Surgical total parathyroidectomy with forearm autografting will be performed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in coronary artery calcium score	Change in coronary artery calcium score	52 weeks
change in left ventricular mass index	change in left ventricular mass index	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in left ventricular volume and ejection fraction	change in left ventricular volume and ejection fraction	52 weeks
Change in aortic pulse wave velocity	Change in aortic pulse wave velocity	24 and 52 weeks
Change in aortic valve and mitral valve calcium score	Change in aortic valve and mitral valve calcium score	52 weeks
change in augmentation index and heart rate adjusted augmentation index	change in augmentation index and heart rate adjusted augmentation index	over 52 weeks
change in bone mineral density at forearm, spine and femur	change in bone mineral density at forearm, spine and femur	52 weeks
Quality of Life (QOL) scores	Kidney Disease Outcome Quality Initiatives (KDOQI QOL domain scores)	52 weeks
change in resting energy expenditure	Change in resting energy expenditure	24 and 52 weeks
change in lean muscle mass	Change in lean muscle mass	52 weeks
change in handgrip strength	Change in handgrip strength	24 and 52 weeks
Change in subjective global assessment	Change in subjective global assessment	24 and 52 weeks
Change in serum calcium and phosphorus	Change in biochemical parameter Serum calcium and phosphorus	over 52 weeks
change in intact parathyroid hormone (iPTH) level	Change in biochemical parameter Parathyroid hormone	52 weeks
Change in alkaline phosphatase	Change in biochemical parameter alkaline phosphatase	over 52 weeks
change in serum albumin	CHange in biochemical parameter serum albumin	over 52 weeks
change in lymphocyte count	change in lymphocyte count	over 52 weeks
change in lipid profile	change in lipid profile	over 52 weeks
change in systolic and diastolic blood pressure	change in systolic and diastolic blood pressure	over 52 weeks
change in subendocardial viability ratio	change in subendocardial viability ratio	over 52 weeks

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Angela YM Wang, MD, PhD, University of Hong Kong, Queen Mary Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 10, 2010
• Primary Completion (ACTUAL): May 22, 2017
• Study Completion (ACTUAL): May 22, 2017

Study Registration Dates

• First Submitted: October 4, 2011
• First Submitted That Met QC Criteria: October 4, 2011
• First Posted (ESTIMATE): October 6, 2011

Study Record Updates

• Last Update Posted (ACTUAL): October 12, 2021
• Last Update Submitted That Met QC Criteria: October 4, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: chronic kidney disease; peritoneal dialysis; parathyroidectomy; vascular calcification; cinacalcet; secondary hyperparathyroidism
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Neoplasms; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Parathyroid Diseases; Neoplastic Processes; Hyperparathyroidism; Vascular Diseases; Neoplasm Metastasis; Renal Insufficiency; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Calcium-Regulating Hormones and Agents; Calcimimetic Agents; Cinacalcet
• Other Study ID Numbers: CP-2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No