Back to resultsA Pilot Clinical Study Evaluating the Effect of Parathyroid Hormone (PTH) Lowering On Erythropoietin Consumption in Calcitriol-Resistant Patients
Primary Purpose
Moderate to Severe Secondary Hyperparathyroidism, Stage 5 Chronic Kidney Diseases
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Paricalcitol
Darbepoetin alfa
Sponsored by
About this trial
This is an interventional treatment trial for Moderate to Severe Secondary Hyperparathyroidism focused on measuring Hemodialysis, Chronic kidney disease, Secondary hyperparathyroidism,
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Paricalcitol
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Mean Intact Parathyroid Hormone (iPTH) Level at Baseline and Month 6
Mean Calcium Level at Baseline and Month 6
Mean Phosphorus Level at Baseline and Month 6
Mean Alkaline Phosphatase Level at 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
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
Mean High Sensitivity C-reactive Protein (hsCRP) Level at Baseline and Month 6
Mean Fibroblast Growth Factor-23 (FGF-23) Level at 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.
Full Information
NCT ID
NCT01506947
First Posted
December 28, 2011
Last Updated
July 28, 2021
Sponsor
AbbVie (prior sponsor, Abbott)
1. Study Identification
Unique Protocol Identification Number
NCT01506947
Brief Title
A Pilot Clinical Study Evaluating the Effect of Parathyroid Hormone (PTH) Lowering On Erythropoietin Consumption in Calcitriol-Resistant Patients
Official Title
A Prospective, Non-randomised, Single-arm, Open-Label Pilot Clinical Study Evaluating the Effect of PTH Lowering on Erythropoietin Consumption in Calcitriol-Resistant Patients
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
May 10, 2012 (Actual)
Primary Completion Date
April 7, 2016 (Actual)
Study Completion Date
April 7, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie (prior sponsor, Abbott)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
To evaluate the effect of PTH lowering on erythropoietin consumption in calcitriol-resistant patients with stage 5 chronic kidney disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Moderate to Severe Secondary Hyperparathyroidism, Stage 5 Chronic Kidney Diseases
Keywords
Hemodialysis, Chronic kidney disease, Secondary hyperparathyroidism,
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
65 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Paricalcitol
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Paricalcitol
Other Intervention Name(s)
ABT-358, Zemplar
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Darbepoetin alfa
Intervention Description
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.
Primary Outcome Measure Information:
Title
Mean Erythropoietin Dose Per Visit
Description
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.
Time Frame
Baseline and Months 1, 2, 3, 4, 5 and 6
Secondary Outcome Measure Information:
Title
Mean Scores of Short Form Health Survey 36 (SF-36) Questionnaire
Description
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.
Time Frame
Baseline and Month 6
Title
Mean Intact Parathyroid Hormone (iPTH) Level at Baseline and Month 6
Time Frame
Baseline and Month 6
Title
Mean Calcium Level at Baseline and Month 6
Time Frame
Baseline and Month 6
Title
Mean Phosphorus Level at Baseline and Month 6
Time Frame
Baseline and Month 6
Title
Mean Alkaline Phosphatase Level at Baseline and Month 6
Time Frame
Baseline and Month 6
Title
Vitamin B12 Levels
Description
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
Time Frame
Baseline and month 6
Title
Folic Acid Levels
Description
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
Time Frame
Baseline and month 6
Title
Mean High Sensitivity C-reactive Protein (hsCRP) Level at Baseline and Month 6
Time Frame
Baseline and Month 6
Title
Mean Fibroblast Growth Factor-23 (FGF-23) Level at Baseline and Month 6
Time Frame
Baseline and Month 6
Title
Number of Participants With Adverse Events
Description
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.
Time Frame
From the time of study drug administration until 4 weeks after the discontinuation of the study drug; up to 7 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mahmut Gücük, MD
Organizational Affiliation
AbbVie
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
26778412
Citation
Poordad F, Landis CS, Asatryan A, Jackson DF 3rd, Ng TI, Fu B, Lin CW, Yao B, Kort J. High antiviral activity of NS5A inhibitor ABT-530 with paritaprevir/ritonavir and ribavirin against hepatitis C virus genotype 3 infection. Liver Int. 2016 Aug;36(8):1125-32. doi: 10.1111/liv.13067. Epub 2016 Feb 3.
Results Reference
background
Links:
URL
http://rxabbvie.com
Description
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A Pilot Clinical Study Evaluating the Effect of Parathyroid Hormone (PTH) Lowering On Erythropoietin Consumption in Calcitriol-Resistant Patients
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