MedDRA version: 21.0 Level: LLT Classification code 10060881 Term: Adynamic bone disease System Organ Class: 100000004859
Conditions
Interventions
Trade Name: Terrosa 20 micrograms/80 microliters solution for injection
Pharmaceutical Form: Solution for injection
INN or Proposed INN: TERIPARATIDE
CAS Number: 52232-67-4
Concentration unit: µg/µl m
Sponsors
Department of Nephrology, Herlev & Gentofte Hospital, Herlev Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Age =18 years ? CKD stage 4-5D (eGFR =2930 ml/min) according to KDIGO (Kidney Disease Improving Global Outcome) definition ? DEXA scan with a T-score at the total hip, femoral neck or lumbar spine (L1-4) =-2 (or Z-score =-2) in a minimum of 2 vertebraes and/or former fragility fracture (vertebral, hip, for- or upper arm, ankle) assessed with VFA or x-ray of the columna ? Patients with expected adynamic bone disorder, based on BSAP=21 µg/l or biopsy-verified low bone turnover Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 33 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 33
Exclusion criteria
Exclusion criteria: ? Hypercalcemia defined as sustained ionized calcium >1.35 mmol/l ? Previous fracture within the last 6 months * Patients may be rescreened after the 6 months ? Previous calciphylaxis ? Thyroid disturbances not adequately treated based on the opinion by the clinician ? Treatment with digoxin ? Paget’s disease or other metabolic bone disorders ? Antiresorptive or bone anabolic medication during the last 24 months (for bisphosphonates it is only during the last 12 months) ? Former or present malignant disease (except skin basal or planocellular carcinoma) ? Previous external beam or implant radiation therapy to the skeleton ? Kidney transplanted patients ? Oral prednisolone treatment exceeding a total of 450 mg during the last 6 months or active oral prednisolone treatment with a daily dose of > 5 mg ? 25 hydroxyvitamin D2 and D3 3x upper limit of normal or bilirubin > 2x upper limit of normal ? Pregnancy, lactation or fertile women * Post-menopausal females are not considered fertile not using safe anticonception (the following contraceptive methods are considered appropriate: Intrauterine device (IUD) or hormonal anticontraceptive (oral contraceptives, implant, transdermal patches, vaginal ring or depot injection)). ? Hypersensitivity to the active substance in teriparatide or to any of the excipients or content ? Inability to provide informed consent ? Medical conditions or treatments that may interfere with assessments of the outcomes of the trial ? Drug or alcohol abuse ? Unable to participate in a clinical study based on the judgement by the local investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The study will explore if treatment with recombinant human parathyroid hormone (PTH) improves bone turnover and bone mineral density (BMD) and thereby prevent the high risk of fracture in patients with chronic kidney disease (CKD). ;Secondary Objective: Disturbed bone metabolism is related to increased risk of cardiovascular disease in patients with CKD. The study will examine if treatment with recombinant PTH improves cardiovascular parameters. ;Primary end point(s): The primary endpoint is the difference between the two groups (treated versus controls) in changes in BSAP after 18 months. ;Timepoint(s) of evaluation of this end point: Evalutaion of this endpoint is after 18 months after inclusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Changes between baseline and 18 months as well as differences between treated and untreated in: ? Number of patients who no longer have adynamic bone disorder based on a BSAP >21 µg/l ? BMD at the lumbar spine, antebrachium, femoral neck and total hip ? Incidence of fragility fractures and vertebral fractures assessed using vertebral fracture assessment (VFA) or x-ray of columna ? Bone microarchitecture, volumetric BMD, bone geometry and bone strength assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) ? Regional bone formation using 18F-NAF PET/CT ? P-parathyroid hormone (intact, whole and nonoxidated-PTH), p-ionised calcium, p-phosphate, p-magnesium, p-FGF-23 and p-sclerostin ? Bone microstructure by micro-computer tomography (µCT) of the bone biopsy ? Static and dynamic bone histomorphometry classified by the TMV classification assessed by bone biopsy ? Detailed histology of underSlying cellular mechanisms using a combination of immunostainings and advanced in situ hybridizations on the bone biopsy ? Bone turnover markers i.e. intact PINP, TRAP5b, osteocalcin, RANKL and OPG ? 24-hour blood pressure and pulse wave measurements including velocity ? T50 (30), NT-proBNP as well as other cardiovascular biomarkers ? The incidence of adverse reactions ;Timepoint(s) of evaluation of this end point: After 18 months after inclusion and for some also after 30 months after inclusion (DEXA, X-ray, blood samples) | — |
Countries
Denmark
Contacts
Public ContactResarch unit, Nephrology
Herlev & Gentofte Hospital
Outcome results
None listed