Study to Evaluate the Effect of Intravenous (IV) Paricalcitol (Zemplar) on Cardiac Morbidity in Patients With Chronic Kidney Disease (CKD) Stage 5 Over 2 Years

• Sponsor: AbbVie (prior sponsor, Abbott) (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01073462
• Collaborator: Assign Data Management and Biostatistics GmbH (Other)
• Enrollment: 67
• Locations: 12
• Duration (Months): 54
• Patients Per Site: 5.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study was to ascertain the percentage of cardiac patients with chronic kidney disease (CKD) stage 5 treated with paricalcitol IV achieving intact parathyroid hormone (iPTH) levels in target range of Kidney Disease Outcomes Quality Initiative (K/DOQI) treatment guidelines (150 - 300 pg/mL) after 2 years.

Condition or Disease	Intervention/Treatment	Phase
Secondary Hyperparathyroidism; Chronic Kidney Disease Stage V; Cardiac Morbidity

Detailed Description

Secondary hyperparathyroidism (SHPT) is a frequent complication in patients with chronic kidney disease (CKD) stage 5 receiving dialysis. SHPT is an adaptive response to CKD and is characterized by an elevation in parathyroid hormone (PTH) and consecutively high calcium levels. Elevations in calcium levels, phosphate levels, and PTH are correlated with CKD disease progression as well as development or aggravation of cardiovascular impairment. Many CKD patients cannot be treated well with Vitamin D analogues because of effects on calcium. Hypercalcemia is a well - known factor for cardiac disease. No data are available in Austria for a cohort with cardiac disease treated with Zemplar (paricalcitol IV).

Study Design

• Study Type: Observational
• Actual Enrollment: 67 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Postmarketing Observational Study to Evaluate the Effect of Zemplar (Paricalcitol IV) on Cardiac Morbidity in Patients With Chronic Kidney Disease Stage 5 Over 2 Years.
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Paricalcitol IV Participants with chronic kidney disease stage 5 with secondary hyperparathyroidism and cardiac morbidity received intravenous (IV) paricalcitol (Zemplar) prescribed according to current practice with regards to dose, population and indication for up to 2 years.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving an Intact Parathyroid Hormone (iPTH) Level Within the Target Range [Baseline and Months 3, 6, 12, 18, and 24]

   Target range of intact parathyroid hormone was defined according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) treatment guidelines as between 15.9 - 31.8 pmol/L (150 to 300 pg/mL).

Secondary Outcome Measures

1. Percentage of Participants With Hypercalcemia [Baseline and Months 3, 6, 12, 18, and 24]

   Hypercalcemia was defined as a calcium value of > 2.625 mmol/L (10.5 mg/dL) in one measurement. Serum calcium was measured at every study visit.

2. Percentage of Participants With Hyperphosphatemia [Baseline and Months 3, 6, 12, 18, and 24]

   Hyperphosphatemia was defined as a phosphate value of > 2.1 mmol/L (6.5 mg/dL) in one measurement. Serum phosphate was measured at every study visit.

3. Percentage of Participants With at Least a 30%-Reduction in iPTH Levels [Baseline and Months 3, 6, 12, 18, and 24]

   The percentage of participants with at least a 30% reduction in intact parathyroid hormone (iPTH) levels from Baseline level.

4. Percentage of Participants With at Least 30%-Reduction in iPTH Levels in at Least Two Consecutive Measurements [Baseline to Month 24]

   The percentage of participants with at least a 30% reduction in intact parathyroid hormone (iPTH) level from Baseline in at least 2 consecutive visits.

5. Percentage of Participants With at Least One Concomitant Medication [24 months]

   The percentage of participants with at least one concomitant medication during the course of the study, by the following types: Phosphate binder Epoetin Renin-Angiotensin-Aldosterone System (RAAS) inhibitors Cinacalcet Other

6. Percentage of Participants Experiencing Hospitalization [24 months]

   The percentage of participants with at least one hospitalization, at least one cardiac-related hospitalization and at least one non-cardiac-related hospitalization during the course of the study.

7. Number of Participants With Cardiac Disease Progression [Month 3, 6, 12, 18, and 24]

   Cardiac disease progression was determined by the Investigator.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients aged at least 18 years

• Patients with secondary hyperparathyroidism associated with CKD stage 5, serum iPTH > 150 pg/mL,

• Cardiac disease as described by Medical Dictionary for Regulatory Activities (MedDRA) terms:

• cardiac disorder as cardiac arrhythmias

• cardiac disorder signs and symptoms

• cardiac neoplasm

• cardiac valve disorder

• heart failures

• myocardial disorder

• pericardial disorder

• Serum phosphate level < 6.5 mg/dL and serum calcium level < 10.5 mg/dL

Exclusion Criteria:

• Patients who meet contraindications as outlined in the latest version of Zemplar (Paricalcitol IV) summary of product characteristics

• Patients with known hypersensitivity to paricalcitol or any component of the formulation, vitamin D intoxication, hypercalcemia; cinacalcet as concomitant medication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site Reference ID/Investigator# 27447	Graz		Austria	8010
2	Site Reference ID/Investigator# 49182	Graz		Austria	8020
3	Site Reference ID/Investigator# 27483	Graz		Austria	80360
4	Site Reference ID/Investigator# 52742	Graz		Austria	8052
5	Site Reference ID/Investigator# 27487	Innsbruck		Austria	6020
6	Site Reference ID/Investigator# 36983	Linz		Austria	4010
7	Site Reference ID/Investigator# 27484	Linz		Austria	4020
8	Site Reference ID/Investigator# 27485	Rottenmann		Austria	8786
9	Site Reference ID/Investigator# 27446	Vienna		Austria	1030
10	Site Reference ID/Investigator# 53469	Vienna		Austria	1090
11	Site Reference ID/Investigator# 27482	Vienna		Austria	1130
12	Site Reference ID/Investigator# 10981	Vienna		Austria	1220

Sponsors and Collaborators

• AbbVie (prior sponsor, Abbott)
• Assign Data Management and Biostatistics GmbH

Investigators

• Study Director: Astrid Dworan-Timler, AbbVie Austria

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: AbbVie (prior sponsor, Abbott)
• ClinicalTrials.gov Identifier: NCT01073462
• Other Study ID Numbers: P10-680
• First Posted: Feb 23, 2010
• Last Update Posted: Jul 10, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by AbbVie (prior sponsor, Abbott): Secondary Hyperparathyroidism (sHPT); Paricalcitol; Chronic kidney disease stage 5 (CKD stage 5)
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Hyperparathyroidism, Secondary

Study Results

Participant Flow

Arm/Group Title	Paricalcitol IV
Arm/Group Description	Participants with chronic kidney disease stage 5 with secondary hyperparathyroidism and cardiac morbidity received intravenous (IV) paricalcitol (Zemplar) prescribed according to current practice with regards to dose, population and indication for up to 2 years.
Period Title: Overall Study
STARTED	67
COMPLETED	26
NOT COMPLETED	41

Baseline Characteristics

Arm/Group Title	Paricalcitol IV
Arm/Group Description	Participants with chronic kidney disease stage 5 with secondary hyperparathyroidism and cardiac morbidity received intravenous (IV) paricalcitol (Zemplar) prescribed according to current practice with regards to dose, population and indication for up to 2 years.
Overall Participants	67
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.5 (13.8)
Sex: Female, Male (Count of Participants)
Female	27 40.3%
Male	40 59.7%
Region of Enrollment (participants) [Number]
Austria	67 100%
Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Systolic	137.2 (19.4)
Diastolic	75.1 (11.5)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving an Intact Parathyroid Hormone (iPTH) Level Within the Target Range
Description	Target range of intact parathyroid hormone was defined according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) treatment guidelines as between 15.9 - 31.8 pmol/L (150 to 300 pg/mL).
Time Frame	Baseline and Months 3, 6, 12, 18, and 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat population; last observation carried forward (LOCF) imputation was used.

Arm/Group Title	Paricalcitol IV
Arm/Group Description	Participants with chronic kidney disease stage 5 with secondary hyperparathyroidism and cardiac morbidity received intravenous (IV) paricalcitol (Zemplar) prescribed according to current practice with regards to dose, population and indication for up to 2 years.
Measure Participants	67
Baseline	28.4 42.4%
Month 3	43.3 64.6%
Month 6	35.8 53.4%
Month 12	38.8 57.9%
Month 18	37.3 55.7%
Month 24	35.8 53.4%

2. Secondary Outcome

Title	Percentage of Participants With Hypercalcemia
Description	Hypercalcemia was defined as a calcium value of > 2.625 mmol/L (10.5 mg/dL) in one measurement. Serum calcium was measured at every study visit.
Time Frame	Baseline and Months 3, 6, 12, 18, and 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat; LOCF was used

Arm/Group Title	Paricalcitol IV
Arm/Group Description	Participants with chronic kidney disease stage 5 with secondary hyperparathyroidism and cardiac morbidity received intravenous (IV) paricalcitol (Zemplar) prescribed according to current practice with regards to dose, population and indication for up to 2 years.
Measure Participants	67
Baseline	0.0 0%
Month 3	0.0 0%
Month 6	0.0 0%
Month 12	1.5 2.2%
Month 18	0.0 0%
Month 24	1.5 2.2%

3. Secondary Outcome

Title	Percentage of Participants With Hyperphosphatemia
Description	Hyperphosphatemia was defined as a phosphate value of > 2.1 mmol/L (6.5 mg/dL) in one measurement. Serum phosphate was measured at every study visit.
Time Frame	Baseline and Months 3, 6, 12, 18, and 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat; LOCF was used. "n" indicates the number of participants with available data at each time point.

Arm/Group Title	Paricalcitol IV
Arm/Group Description	Participants with chronic kidney disease stage 5 with secondary hyperparathyroidism and cardiac morbidity received intravenous (IV) paricalcitol (Zemplar) prescribed according to current practice with regards to dose, population and indication for up to 2 years.
Measure Participants	67
Baseline (n=65)	0.0 0%
Month 3 (n=67)	28.4 42.4%
Month 6 (n=67)	31.3 46.7%
Month 12 (n=67)	25.4 37.9%
Month 18 (n=67)	23.9 35.7%
Month 24 (n=67)	22.4 33.4%

4. Secondary Outcome

Title	Percentage of Participants With at Least a 30%-Reduction in iPTH Levels
Description	The percentage of participants with at least a 30% reduction in intact parathyroid hormone (iPTH) levels from Baseline level.
Time Frame	Baseline and Months 3, 6, 12, 18, and 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat; LOCF was used.

Arm/Group Title	Paricalcitol IV
Arm/Group Description	Participants with chronic kidney disease stage 5 with secondary hyperparathyroidism and cardiac morbidity received intravenous (IV) paricalcitol (Zemplar) prescribed according to current practice with regards to dose, population and indication for up to 2 years.
Measure Participants	67
Month 3	41.8 62.4%
Month 6	40.3 60.1%
Month 12	47.8 71.3%
Month 18	52.2 77.9%
Month 24	47.8 71.3%

5. Secondary Outcome

Title	Percentage of Participants With at Least 30%-Reduction in iPTH Levels in at Least Two Consecutive Measurements
Description	The percentage of participants with at least a 30% reduction in intact parathyroid hormone (iPTH) level from Baseline in at least 2 consecutive visits.
Time Frame	Baseline to Month 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Paricalcitol IV
Arm/Group Description	Participants with chronic kidney disease stage 5 with secondary hyperparathyroidism and cardiac morbidity received intravenous (IV) paricalcitol (Zemplar) prescribed according to current practice with regards to dose, population and indication for up to 2 years.
Measure Participants	67
Number [percentage of participants]	44.8 66.9%

6. Secondary Outcome

Title	Percentage of Participants With at Least One Concomitant Medication
Description	The percentage of participants with at least one concomitant medication during the course of the study, by the following types: Phosphate binder Epoetin Renin-Angiotensin-Aldosterone System (RAAS) inhibitors Cinacalcet Other
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Paricalcitol IV
Arm/Group Description	Participants with chronic kidney disease stage 5 with secondary hyperparathyroidism and cardiac morbidity received intravenous (IV) paricalcitol (Zemplar) prescribed according to current practice with regards to dose, population and indication for up to 2 years.
Measure Participants	67
Phosphate binder	80.6 120.3%
Epoetin	68.7 102.5%
RAAS Inhibitor	43.3 64.6%
Cinacalcet	13.4 20%
Other	86.6 129.3%

7. Secondary Outcome

Title	Percentage of Participants Experiencing Hospitalization
Description	The percentage of participants with at least one hospitalization, at least one cardiac-related hospitalization and at least one non-cardiac-related hospitalization during the course of the study.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Paricalcitol IV
Arm/Group Description	Participants with chronic kidney disease stage 5 with secondary hyperparathyroidism and cardiac morbidity received intravenous (IV) paricalcitol (Zemplar) prescribed according to current practice with regards to dose, population and indication for up to 2 years.
Measure Participants	67
Hospitalizations	41.8 62.4%
Cardiac-related hospitalizations	14.9 22.2%
Non-cardiac-related hospitalizations	37.3 55.7%

8. Secondary Outcome

Title	Number of Participants With Cardiac Disease Progression
Description	Cardiac disease progression was determined by the Investigator.
Time Frame	Month 3, 6, 12, 18, and 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Paricalcitol IV
Arm/Group Description	Participants with chronic kidney disease stage 5 with secondary hyperparathyroidism and cardiac morbidity received intravenous (IV) paricalcitol (Zemplar) prescribed according to current practice with regards to dose, population and indication for up to 2 years.
Measure Participants	67
Month 3	2 3%
Month 6	2 3%
Month 12	4 6%
Month 18	0 0%
Month 24	0 0%

Adverse Events

Time Frame	24 months
Arm/Group Title	Paricalcitol IV
Arm/Group Description	Participants with chronic kidney disease stage 5 with secondary hyperparathyroidism and cardiac morbidity received intravenous (IV) paricalcitol (Zemplar) prescribed according to current practice with regards to dose, population and indication for up to 2 years
All Cause Mortality
	Paricalcitol IV
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Paricalcitol IV
	Affected / at Risk (%)	# Events
Total	31/67 (46.3%)
Cardiac disorders
Cardiac failure	3/67 (4.5%)
Myocardial infarction	3/67 (4.5%)
Coronary artery disease	2/67 (3%)
Arrhythmia	1/67 (1.5%)
Atrial fibrillation	1/67 (1.5%)
Cardiac arrest	1/67 (1.5%)
Cardiogenic shock	1/67 (1.5%)
Pericardial effusion	1/67 (1.5%)
Pericarditis	1/67 (1.5%)
Sinus bradycardia	1/67 (1.5%)
Supraventricular tachycardia	1/67 (1.5%)
Ear and labyrinth disorders
Vertigo	2/67 (3%)
Gastrointestinal disorders
Colitis ischaemic	1/67 (1.5%)
Haemorrhoids	1/67 (1.5%)
Ileus	1/67 (1.5%)
Tooth disorder	1/67 (1.5%)
Vomiting	1/67 (1.5%)
General disorders
Death	3/67 (4.5%)
Infections and infestations
Pneumonia	3/67 (4.5%)
Acute tonsillitis	1/67 (1.5%)
Bronchopneumonia	1/67 (1.5%)
Cystitis	1/67 (1.5%)
Gastroenteritis	1/67 (1.5%)
Infectious pleural effusion	1/67 (1.5%)
Muscle abscess	1/67 (1.5%)
Osteomyelitis	1/67 (1.5%)
Pancreatic abscess	1/67 (1.5%)
Staphylococcal sepsis	1/67 (1.5%)
Tracheobronchitis	1/67 (1.5%)
Urinary tract infection	1/67 (1.5%)
Injury, poisoning and procedural complications
Shunt thrombosis	5/67 (7.5%)
Multiple fractures	1/67 (1.5%)
Post procedural haemorrhage	1/67 (1.5%)
Metabolism and nutrition disorders
Hypokalaemia	1/67 (1.5%)
Nervous system disorders
Cerebral haemorrhage	2/67 (3%)
Carotid artery stenosis	1/67 (1.5%)
Polyneuropathy	1/67 (1.5%)
Renal and urinary disorders
Renal failure	1/67 (1.5%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	2/67 (3%)
Dyspnoea	2/67 (3%)
Epistaxis	1/67 (1.5%)
Haemoptysis	1/67 (1.5%)
Skin and subcutaneous tissue disorders
Panniculitis	1/67 (1.5%)
Surgical and medical procedures
Knee arthroplasty	1/67 (1.5%)
Medical device implantation	1/67 (1.5%)
Stent placement	1/67 (1.5%)
Surgery	1/67 (1.5%)
Vascular disorders
Hypertensive crisis	1/67 (1.5%)
Peripheral arterial occlusive disease	1/67 (1.5%)
Other (Not Including Serious) Adverse Events
	Paricalcitol IV
	Affected / at Risk (%)	# Events
Total	23/67 (34.3%)
Cardiac disorders
Cardiac valve disease	1/67 (1.5%)
Ear and labyrinth disorders
Vertigo	1/67 (1.5%)
Gastrointestinal disorders
Abdominal pain	1/67 (1.5%)
Coeliac artery stenosis	1/67 (1.5%)
Infections and infestations
Herpes zoster	1/67 (1.5%)
Pneumonia	1/67 (1.5%)
Respiratory tract infection	1/67 (1.5%)
Urinary tract infection	1/67 (1.5%)
Injury, poisoning and procedural complications
Procedural hypotension	1/67 (1.5%)
Metabolism and nutrition disorders
Hyperphosphataemia	16/67 (23.9%)
Hyperkalaemia	1/67 (1.5%)
Nervous system disorders
Dysgeusia	1/67 (1.5%)
Headache	1/67 (1.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.