Ignite Creation Date:
2025-12-24 @ 6:44 PM
Ignite Modification Date:
2026-03-24 @ 10:55 AM
Study NCT ID:
NCT06352957
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-04-08
First Post:
2024-03-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Use of ETElcalcetidefor pReserving vitamiN K-dependent proteIn activiTY ITAlian Study
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D061205', 'term': 'Vascular Calcification'}, {'id': 'D050723', 'term': 'Fractures, Bone'}], 'ancestors': [{'id': 'D002114', 'term': 'Calcinosis'}, {'id': 'D002128', 'term': 'Calcium Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D014947', 'term': 'Wounds and Injuries'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 160}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2024-05-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-03', 'completionDateStruct': {'date': '2027-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-04-03', 'studyFirstSubmitDate': '2024-03-21', 'studyFirstSubmitQcDate': '2024-04-03', 'lastUpdatePostDateStruct': {'date': '2024-04-08', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-04-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Levels of VKDP', 'timeFrame': 'Baseline and after 3, 9, and 18 months of treatment', 'description': '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).'}], 'secondaryOutcomes': [{'measure': 'Calcium', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of calcium (mg/dL)'}, {'measure': 'Phosphate', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of phosphate (mg/dL)'}, {'measure': 'Magnesium', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of magnesium (mg/dL)'}, {'measure': 'ALP', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of ALP (U/L)'}, {'measure': 'PTH', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of PTH (pg/ml)'}, {'measure': '25(OH)D', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of 25(OH)D (ng/mL)'}, {'measure': 'P1NP', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of Procollagen I Intact N-Terminal or P1NP (ug/L )'}, {'measure': 'CTX', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of C-terminal telopeptide or CTX (pg/mL)'}, {'measure': 'TRAP 5b', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of Tartrate-resistant acid phosphatase 5b or TRAP 5bC-Terminal to Intact (U/L)'}, {'measure': 'BSAP', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of Bone-specific alkaline phosphatase or BSAP (mcg/L)'}, {'measure': 'cFGF23', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of Fibroblast Growth Factor 23 or cFGF23 (pmol/L) and iFGF23 (pg/mL)'}, {'measure': 'Klotho', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of Klotho (pg/mL) and soluble α-Klotho (pg/mL)'}, {'measure': 'Sclerostin', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of Sclerostin and Bioactive Sclerostin (pmol/L)'}, {'measure': 'DKK1', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of DKK1 (pmol/L)'}, {'measure': 'Fetuin A', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of Fetuin A (ng/mL)'}, {'measure': 'Zinc', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of Zinc (μmol/L)'}, {'measure': 'Irisin', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of Irisin'}, {'measure': 'Serum Calcification Propensity T50 test', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Serum Calcification Propensity T50 test (minutes)'}, {'measure': 'Hemoglobin (Hb)', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of Hemoglobin (g/dl)'}, {'measure': 'Hematocrit (Ht)', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of Hematocrit (%)'}, {'measure': 'Plates (PLTS)', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of plates (g/L)'}, {'measure': 'Reticulocytes', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of reticulocytes (%)'}, {'measure': 'Iron', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of iron (µg/dL)'}, {'measure': 'Ferritin', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of ferritin (ng/ml )'}, {'measure': 'Transferrin', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of transferrin (mg/dL)'}, {'measure': 'Transferrin Saturation', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Transferrin saturation (%)'}, {'measure': 'Albumin', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of Albumin (g/dl)'}, {'measure': 'KT/V', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Level of KT/V'}, {'measure': 'Aluminium', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of aluminium (mcg/L)'}, {'measure': 'C-reactive Protein (CRP)', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of C-reactive Protein (mg/L)'}, {'measure': 'Cholesterol', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of cholesterol (mg/dl)'}, {'measure': 'Triglycerides', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of triglycerides (mg/dl)'}, {'measure': 'Cholesterol HDL', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of Cholesterol HDL (mg/dl)'}, {'measure': 'Cholesterol LDL', 'timeFrame': 'Baseline, 3, 9 and 18-months', 'description': 'Concentration of Cholesterol LDL (mg/dl)'}, {'measure': 'Vascular Calcification', 'timeFrame': 'Baseline, 18-months', 'description': 'Number of participants with vascular calcification (Aorta and Iliac arteries) by lateral Dorsal Lumbar spine x-Ray.'}, {'measure': 'Vertebral Fractures', 'timeFrame': 'Baseline, 18-months', 'description': 'Changes from baseline prevalence Vertebral Fractures (VFs, quantitative vertebral morphometry using dedicated software) by lateral Dorsal Lumbar spine x-Ray'}, {'measure': 'BMD: Bone Mineral Density', 'timeFrame': 'Baseline, 18-months', 'description': 'Changes from baseline Total Hip, Femoral neck Bone Mass Density (BMD) by Dual-energy X-ray absorptiometry (DEXA) including Trabecular Bone Score where it will be available (TBS).'}, {'measure': 'Association between Verterbal Fractures and Vascular Calcificatiom', 'timeFrame': 'Baseline, 18-months', 'description': 'To evaluate the relationship of bone vascular biomarkers on clinical outcomes: VFs and VCs'}, {'measure': 'Novel quantitative computer-assisted scoring method for vascular calcifications.', 'timeFrame': 'Baseline, 18-months', 'description': 'To compare a novel quantitative computer-assisted scoring method for vascular calcifications with a three-dimensional assessment from CT data'}, {'measure': 'Effect of Etelcalcetide on cardiovascular events and all-cause mortality.', 'timeFrame': 'Baseline, 18-months', 'description': 'Effect of Etelcalcetide on the number of cardiovascular events and on the number of all-cause deaths.'}, {'measure': 'Etelcalcetide Safety: Number of participants with treatment-related adverse events.', 'timeFrame': 'Baseline, 18-months', 'description': 'The outcome can identify potential adverse events, such as: Blood calcium decrease, Muscle spasms, Diarrhea, Nausea, Vomiting, Headache, Hypocalcaemia, Hypertension, Hypotension, Arteriovenous fistula site complication, Pain in extremity, Paresthesia, Back pain, Upper respiratory tract infection.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Hemodialysis', 'Matrix Gla protein', 'Osteocalcin or Bone GLA Protein (BGP)', 'Vascular calcification', 'Vitamin K', 'Etecalcetide', 'Bone Fractures'], 'conditions': ['Hemodialysis']}, 'descriptionModule': {'briefSummary': '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.\n\nThe 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.', 'detailedDescription': 'Vascular calcifications (VCs) are frequent complications of chronic kidney disease (CKD), and mineral disorders are associated with aortic calcifications and increased risk of bone fractures. The complex pathogenesis of VCs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key inhibitors, such as vitamin K-dependent proteins (VKDPs) like matrix Gla protein (MGP) play pivotal roles in VCs development. Traditional treatments to reduce VC focus on lowering PTH, calcium and phosphorus levels and etelcalcetide revealed as a promising therapy to this scope. Accordingly, the VItamin K Italian study (VIKI) reported that calcimimetics treated hemodialysis patients had higher levels of total BGP and MGP versus those untreated, suggesting a protective effect of this drugs class. These findings point out the multifactorial nature of VC in CKD and suggest new treatment strategies and targeted pathways for improving outcomes. The ETERNITY-ITA study will investigate the real world effect of Etelcalcetide in increasing actives form VKDPs levels such as BGP and MGP thus contributing to bone and vascular health in hemodialysis patients. ETERNITY-ITA is a multi-center comparative effectiveness, observational, longitudinal study. 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Hemodialysis patients', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Patient has provided informed consent;\n2. Patient is 18 years of age or older of both gender;\n3. Patients receiving maintenance HD three times per week (Kt/V \\>1.2);\n4. Parathyroid hormone concentrations \\>500 ng/l at screening, or if parathyroidectomy is planned or expected, Ca \\>8.3 mg/dl;\n5. Will be considered patients in the exposed group:\n\n 1. Patients who have started Etelcalcetide within 1-month before the study enrolment;\n 2. Patients naïve to intravenous calcimimetics use;\n 3. Patients who have suspended oral calcimimetics from at least 1-month;\n 4. Patients who are not responder or not compliant to the treatment with calcitriol;\n6. 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;\n7. Native vitamin D can be used in both groups and should be administered to target a 25(OH)D level \\> 30 ng/ml;\n8. Dialysate calcium concentration must be stable for at least 4 weeks prior to screening laboratory assessments;\n9. 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);\n10. 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;\n11. 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.\n\nExclusion Criteria:\n\n1. 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;\n2. Patients has received a bisphosphonate, denosumab or teriparatide during the 12 months prior to screening;\n3. The patient underwent parathyroidectomy in the 6 months before the start of the study or if scheduled soon;\n4. Scheduled kidney transplant during the study period or anticipated living donor evaluation within three months of recruitment;\n5. 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;\n6. Metabolic bone diseases not related to the kidney (i.e., Pagets, Osteogenesis Imprefecta);\n7. Severe untreated hyperthyroidism;\n8. Malignancy within the last 3 years (except non-melanoma skin cancers or cervical carcinoma in situ);\n9. Patient is pregnant or nursing;\n10. Patients with Long QT Syndrome;\n11. 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."}, 'identificationModule': {'nctId': 'NCT06352957', 'acronym': 'ETERNITY-ITA', 'briefTitle': 'Use of ETElcalcetidefor pReserving vitamiN K-dependent proteIn activiTY ITAlian Study', 'organization': {'class': 'OTHER', 'fullName': 'Istituto di Fisiologia Clinica CNR'}, 'officialTitle': 'Use of ETElcalcetidefor pReserving vitamiN K-dependent proteIn activiTY ITAlian Study', 'orgStudyIdInfo': {'id': '23022022CERC'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Etecalcetide Group', 'description': "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.\n\nOther Name: Parsabiv"}, {'label': 'Standard of Care', 'description': 'Drug: Vitamin D or Vitamin D analogs'}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Maria Fusaro, MD', 'role': 'CONTACT', 'email': 'dante.lucia11@gmail.com', 'phone': '0965393253'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Istituto di Fisiologia Clinica CNR', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}