Use of ETElcalcetidefor pReserving vitamiN K-dependent proteIn activiTY ITAlian Study

NCT06352957 | Not Yet Recruiting DMC

• 1 other identifier: 23022022CERC
• Study Type: observational
• Target: 160
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this Prospective Observational Study of comparative effectiveness is to provide real world evidence of the effect of Etelcalcetide in increasing actives form VKDPs levels such as BGP and MGP at 3, 9 and 18 months from baseline, with resulting correct bone mineralization and inhibition vascular calcification in hemodialysis patients. The study will enroll 160 hemodialysis patients: 80 patients treated with Etelcalcetide and 80 age and sex matched patients treated with Calcitriol or vitamin D analogs. The treating nephrologist will base the target dose of Etelcalcetide on individual-level in order to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). The main endpoint is the comparison of the levels of active forms of VKDP (MGP and BGP) between patients treated with Etelcalcetide and those treated with vitamin D or vitamin D analogues. The measurements of the biomarkers are scheduled at baseline and after 3, 9, and 18 months.

Conditions

Hemodialysis

Keywords

Hemodialysis; Matrix Gla protein; Osteocalcin or Bone GLA Protein (BGP); Vascular calcification; Vitamin K; Etecalcetide; Bone Fractures

Outcome Measures

Primary Outcomes (1)

• Levels of VKDP

  The primary endpoint is the comparison of the levels of active forms of VKDP between patients treated with Etelcalcetide and those treated with vitamin D or vitamin D analogues (MGP and BGP).

  Baseline and after 3, 9, and 18 months of treatment

Secondary Outcomes (41)

• Calcium

  Baseline, 3, 9 and 18-months

• Phosphate

  Baseline, 3, 9 and 18-months

• Magnesium

  Baseline, 3, 9 and 18-months

• ALP

  Baseline, 3, 9 and 18-months

• PTH

  Baseline, 3, 9 and 18-months

Study Arms (2)

Etecalcetide Group

Drug: Etelcalcetide Administered intravenously at the end of each dialysis session. Dosing ranges from 2.5 mg to 15 mg set by the patient's physician. Other Name: Parsabiv

Standard of Care

Drug: Vitamin D or Vitamin D analogs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Hemodialysis patients

You may qualify if:

• Patient has provided informed consent;
• Patient is 18 years of age or older of both gender;
• Patients receiving maintenance HD three times per week (Kt/V \>1.2);
• Parathyroid hormone concentrations \>500 ng/l at screening, or if parathyroidectomy is planned or expected, Ca \>8.3 mg/dl;
• Will be considered patients in the exposed group:
• Patients who have started Etelcalcetide within 1-month before the study enrolment;
• Patients naïve to intravenous calcimimetics use;
• Patients who have suspended oral calcimimetics from at least 1-month;
• Patients who are not responder or not compliant to the treatment with calcitriol;
• In the unexposed group, patients on treatment with calcitriol or vitamin D analogs and who are age (± 2 years) and sex comparable (matching) to those in the exposed group will be considered;
• Native vitamin D can be used in both groups and should be administered to target a 25(OH)D level \> 30 ng/ml;
• Dialysate calcium concentration must be stable for at least 4 weeks prior to screening laboratory assessments;
• Patient must have severe HPT as defined by two laboratory screening pre-dialysis serum PTH values \> 500 pg/ml, measured on two consecutive lab checks prior to entering the study. PTH levels should be standardized according to the following table (Souberbielle et al. Kidney Int 2010);
• Total alkaline phosphatase greater than the normal range, or even within the normal range but if greater than the tertile of the reference range for the assay;
• Patients will be eligible only if they will show at least a moderate Aorta VCs and/or Iliac arteries VCs and at least a mild VF.

You may not qualify if:

• Previous treatment with oral calcimimetics (cinacalcet) must have been suspended for at least 30 days. Recent start of calcimimetics (Etelcalcetide) is acceptable, but patients are excluded if treatment lasts for more than 1 month;
• Patients has received a bisphosphonate, denosumab or teriparatide during the 12 months prior to screening;
• The patient underwent parathyroidectomy in the 6 months before the start of the study or if scheduled soon;
• Scheduled kidney transplant during the study period or anticipated living donor evaluation within three months of recruitment;
• Patient has an unstable medical condition based on medical history, physical examination, and routine laboratory tests, or is otherwise unstable in the judgment of the Investigator;
• Metabolic bone diseases not related to the kidney (i.e., Pagets, Osteogenesis Imprefecta);
• Severe untreated hyperthyroidism;
• Malignancy within the last 3 years (except non-melanoma skin cancers or cervical carcinoma in situ);
• Patient is pregnant or nursing;
• Patients with Long QT Syndrome;
• Patient likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the patient and Investigator's knowledge.

Sponsors & Collaborators

• Istituto di Fisiologia Clinica CNR: lead

MeSH Terms

Conditions

Vascular Calcification; Fractures, Bone

Condition Hierarchy (Ancestors)

Calcinosis; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Wounds and Injuries

Central Study Contacts

Maria Fusaro, MD

CONTACT

0965393253; dante.lucia11@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2024
• First Posted: April 8, 2024
• Study Start: May 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 8, 2024

Record last verified: 2024-03