A Pilot Clinical Study Evaluating the Effect of Parathyroid Hormone (PTH) Lowering On Erythropoietin Consumption in Calcitriol-Resistant Patients

Study Overview
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Brief Summary
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To evaluate the effect of PTH lowering on erythropoietin consumption in calcitriol-resistant patients with stage 5 chronic kidney disease.

Official Title
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A Prospective, Non-randomised, Single-arm, Open-Label Pilot Clinical Study Evaluating the Effect of PTH Lowering on Erythropoietin Consumption in Calcitriol-Resistant Patients

Conditions
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Moderate to Severe Secondary Hyperparathyroidism, Stage 5 Chronic Kidney Diseases

Intervention / Treatment
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* Drug: Paricalcitol
* Drug: Darbepoetin alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A subject will only be included if all the following entry criteria are met: Patients ≥ 18 years of age Stage 5 chronic kidney disease (CKD) patients receiving hemodialysis and with moderate to severe secondary hyperparathyroidism (SHPT) Patients with anemia due to renal insufficiency but who are iron replete:; Transferrin saturation (TSAT) > 20% and Ferritin levels > 200 ng/mL and requiring treatment with erythropoietin (EPO) Patients with vitamin B levels > lower limit of normal (LLN) and folic acid levels > LLN Patients treated only with intravenous calcitriol for at least 6 months Patients with serum intact parathyroid hormone (iPTH) level > 500 pg/mL Patients with calcium phosphate product (Ca × PO4) < 65 mg²/dL² Patients willing to sign written informed consents before participating in any the study related activity. Patients with phosphorus levels < 6.5 mg/dL and calcium levels < 11.2 mg/dL Exclusion Criteria: A subject will be excluded from the study if he/she meets any of the following criteria: Patients who have known hypersensitivity and/or toxicity to vitamin D metabolites and/or to paricalcitol and/or to other product ingredients. Patients who have participated in a clinical study within the last month. Patients whose previous concomitant medication and laboratory data for 6 months prior to the baseline visit are not available. Patients with known contraindication to selective Vitamin D receptor activators (VDRAs) according to the Summary of Product Characteristics (SmPC). Pregnancy, breast-feeding or planning a pregnancy within next 6 months after enrollment. Sexually active female patients not accepting appropriate contraceptive methods during the course of the study will also be excluded. Hypertensive and diabetic patients who are not on an optimal and steady medication regimen for more than 30 days. Patients with microcytic (mean corpuscular volume [MCV] < 80 fL) and macrocytic (MCV > 100 fL) anemia at screening that may be caused by diseases such as for microcytic anemias - Iron Deficiency, Thalassemias, Anemia of Chronic Disease, Copper Deficiency, Zinc poisoning, Sideroblastic Anemia, macrocytic anemias -ethanol abuse, myelodysplastic syndromes, acute myeloid leukemias, reticulocytosis, drug induced anemia, liver disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paricalcitol<br>Participants received paricalcitol intravenously during hemodialysis until serum intact parathyroid hormone (iPTH) levels were below 150 pg/mL or for up to 6 months. Paricalcitol dose was based on iPTH levels and was titrated to maintain iPTH levels between 150-300 pg/mL. Participants may have also received routine darbepoetin alfa to treat anemia. | Drug: Paricalcitol<br>* Paricalcitol was administered by intravenous bolus. The initial dose was calculated according to the following formula: [Paricalcitol (µg) = iPTH (pg/mL) / 80]. Subsequent doses were determined based on iPTH, calcium and phosphorus levels.<br>* Other names: Zemplar;Drug: Darbepoetin alfa<br>* Routine darbepoetin alfa use was allowed when transferrin saturation (TSAT) was ≥ 20% and ferritin ≥ 200 μg/L, and hemoglobin level < 11.5 g/dL. The initial dose was 0.25 to 0.75 µg/kg/week, and the maintenance dose was 0.13 to 0.35 µg/kg/week. Target hemoglobin level was between 10 to 11.5 g/dL.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Erythropoietin Dose Per Visit | The requirement of erythropoietin (EPO) treatment to maintain serum hemoglobin levels between 10 to 11.5 g/dL during the study was assessed by analysis of the dose of darbepoetin alfa used at baseline and during each month of the study. The mean EPO dosage per injection for each study month is reported. | Baseline and Months 1, 2, 3, 4, 5 and 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire | The Medical Outcome Study Short Form 36-Item Health Survey (SF-36) is a self-administered questionnaire that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains. The domains include physical (physical functioning, role limitations due to physical health (role-physical), general health perceptions and pain) and mental domains (energy/fatigue (vitality), social functioning, emotional well-being (mental health), and role limitations due to emotional problems (role emotional)). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning. | Baseline and Month 6 | 
| Mean Intact Parathyroid Hormone (iPTH) Level at Baseline and Month 6 |  | Baseline and Month 6 | 
| Mean Calcium Level at Baseline and Month 6 |  | Baseline and Month 6 | 
| Mean Phosphorus Level at Baseline and Month 6 |  | Baseline and Month 6 | 
| Mean Alkaline Phosphatase Level at Baseline and Month 6 |  | Baseline and Month 6 | 
| Vitamin B12 Levels | Vitamin B12 levels were categorized according to the following laboratory reference ranges: Low: < 200 pg/mL Normal: 200 - 950 pg/mL High: > 950 pg/mL | Baseline and month 6 | 
| Folic Acid Levels | Folic acid levels were categorized according to the following laboratory reference ranges: Low: < 4.6 ng/mL Normal: 4.6 - 18.7 ng/mL High: > 18.7 ng/mL | Baseline and month 6 | 
| Mean High Sensitivity C-reactive Protein (hsCRP) Level at Baseline and Month 6 |  | Baseline and Month 6 | 
| Mean Fibroblast Growth Factor-23 (FGF-23) Level at Baseline and Month 6 |  | Baseline and Month 6 | 
| Number of Participants With Adverse Events | Serious adverse events were any adverse events meeting any of the following criteria: An event that resulted in the death of a participant; An event that, in the opinion of the investigator, would have resulted in immediate fatality if medical intervention had not been taken (life-threatening); Resulted in an admission to the hospital for any length of time or prolonged hospital stay; An anomaly detected at or after birth, or any anomaly that results in fetal loss; An event that resulted in a condition that substantially interfered with the activities of daily living; An important medical event that may not be immediately life-threatening or result in death or hospitalization, but based on medical judgment may have jeopardized the participant and may have required medical or surgical intervention to prevent any of the outcomes listed above. Adverse events were assessed by the investigator for possible relationship to study drug. | From the time of study drug administration until 4 weeks after the discontinuation of the study drug; up to 7 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodialysis, Chronic kidney disease, Secondary hyperparathyroidism,