PACE: Paricalcitol Versus Calcitriol for Efficacy and Safety in Stage 3/4 Chronic Kidney Disease (CKD) With Secondary Hyperparathyroidism (SHPT)

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT00823303
• Collaborator: Henry Ford Hospital (Other), Feinberg School of Medicine, Northwestern University (Other), NorthShore University HealthSystem (Other), Abbott (Industry)
• Enrollment: 110
• Locations: 4
• Arms: 2
• Duration (Months): 55
• Patients Per Site: 27.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Secondary Hyperparathyroidism (SHPT) occurs in many patients with kidney disease and leads to bone disease. Active forms of vitamin D, calcitriol and paricalcitol, treat SHPT, but may have different effects on blood calcium. This study will randomize patients with SHPT and stage 3 or 4 CKD to treatment with calcitriol or paricalcitol, and monitor patients for the incidence of high blood calcium, and effectiveness of SHPT treatment.

Condition or Disease	Intervention/Treatment	Phase
Secondary Hyperparathyroidism; Chronic Kidney Disease	Drug: Paricalcitol; Drug: Calcitriol	Phase 4

Detailed Description

General Design

• Open label, active comparator, multicenter, parallel group, phase 4 study of paricalcitol versus calcitriol for suppression of PTH in stage 3 and 4 CKD patients with SHPT.

• Total study duration is 26 weeks (1 week screening, 24 weeks active medications, 1 week follow up.

• Patients meeting inclusion/exclusion criteria including baseline laboratory results will be randomized to paricalcitol or calcitriol, and enter a 24 weeks treatment phase. Visits, including safety and efficacy laboratory tests will be at weeks 4, 8, 12, 18, and 24. A follow up visit will be performed 1 week after stopping study medication.

Study Design

• Study Type: Interventional
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 4 Randomized Multicenter Open Label Trial of Paricalcitol Versus Calcitriol for Efficacy and Safety in Stage 3 or 4 Ckd Patients With Secondary Hyperparathyroidism
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paricalcitol titrated to achieve 40-60% PTH suppression	Drug: Paricalcitol; 1 mcg daily, adjusted to achieve 40-60% PTH suppression; Other Names: Zemplar
Active Comparator: Calcitriol titrated to achieve 40-60% PTH suppression	Drug: Calcitriol; 0.25 mcg daily, adjusted to achieve 40-60% PTH suppression; Other Names: Rocaltrol

Outcome Measures

Primary Outcome Measures

1. Confirmed Hypercalcemia [24 week treatment period]

   Serum Calcium 10.5 mg/dL or higher, confirmed by repeat measurement.

Eligibility Criteria

Criteria

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

Inclusion Criteria

1. Age >18; Able to give informed consent

2. Chronic kidney disease, and estimated GFR 15 to 60 ml/min using the abbreviated MDRD equation

3. intact PTH (iPTH) >120 pg/ml at baseline

4. albumin corrected calcium > 8.5 mg/dL to < 10.0 mg/dL at baseline

5. Phosphorus < 4.6 mg/dL at baseline

6. If on a phosphorus binder; no change in dose within the 4 weeks prior to screening

Exclusion Criteria

1. Receiving any active form of vitamin D within 4 weeks prior to screening (calcitriol, doxercalciferol; paricalcitol; alfacalcidol)

2. Receiving >50,000 IU per month of ergocalciferol or > 1000 IU of cholecalciferol per day within the previous 30 days.

3. history of primary HPT

4. On prednisone > 30 days within the previous 6 months

5. receiving bisphosphonates or calcitonin within the previous 12 months

6. Non-elective hospitalization within the previous 30 days.

7. Expected to initiate dialysis or receive a kidney transplant within the next 6 mo.

8. History of renal or other organ transplant

9. History of parathyroidectomy or previous diagnosis of primary hyperparathyroidism

10. Receiving cinacalcet within 4 weeks prior to screening.

11. An active drug/alcohol dependence or abuse history

12. History of non-compliance with visits or medications that preclude study compliance in the opinion of the investigator

13. Pregnant, or able to become pregnant and unwilling to use a birth control method considered reliable by the principal investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611
2	Northshore University Health System	Evanston	Illinois	United States	60201
3	Henry Ford Hospital	Detroit	Michigan	United States	48202
4	Washington University	St. Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine
• Henry Ford Hospital
• Feinberg School of Medicine, Northwestern University
• NorthShore University HealthSystem
• Abbott

Investigators

• Principal Investigator: Daniel W Coyne, MD, Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daniel W. Coyne, Professor of Medicine, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT00823303
• Other Study ID Numbers: 22095
• First Posted: Jan 15, 2009
• Last Update Posted: Aug 7, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Daniel W. Coyne, Professor of Medicine, Washington University School of Medicine: PTH; Active Vitamin D; hypercalcemia; Chronic Kidney Disease
• Additional relevant MeSH terms: Neoplasm Metastasis; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Hyperparathyroidism, Secondary; Calcitriol

Study Results

Participant Flow

Arm/Group Title	Paricalcitol	Calcitriol
Arm/Group Description	titrated to achieve 40-60% PTH suppression Paricalcitol: 1 mcg daily, adjusted to achieve 40-60% PTH suppression	titrated to achieve 40-60% PTH suppression Calcitriol: 0.25 mcg daily, adjusted to achieve 40-60% PTH suppression
Period Title: Overall Study
STARTED	54	56
COMPLETED	45	45
NOT COMPLETED	9	11

Baseline Characteristics

Arm/Group Title	Paricalcitol	Calcitriol	Total
Arm/Group Description	titrated to achieve 40-60% PTH suppression Paricalcitol: 1 mcg daily, adjusted to achieve 40-60% PTH suppression	titrated to achieve 40-60% PTH suppression Calcitriol: 0.25 mcg daily, adjusted to achieve 40-60% PTH suppression	Total of all reporting groups
Overall Participants	54	56	110
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.6 (13.2)	64.7 (12.6)	65.6 (12.9)
Sex: Female, Male (Count of Participants)
Female	24 44.4%	30 53.6%	54 49.1%
Male	30 55.6%	26 46.4%	56 50.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	33 61.1%	41 73.2%	74 67.3%
White	18 33.3%	14 25%	32 29.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 5.6%	1 1.8%	4 3.6%

Outcome Measures

1. Primary Outcome

Title	Confirmed Hypercalcemia
Description	Serum Calcium 10.5 mg/dL or higher, confirmed by repeat measurement.
Time Frame	24 week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paricalcitol	Calcitriol
Arm/Group Description	titrated to achieve 40-60% PTH suppression Paricalcitol: 1 mcg daily, adjusted to achieve 40-60% PTH suppression	titrated to achieve 40-60% PTH suppression Calcitriol: 0.25 mcg daily, adjusted to achieve 40-60% PTH suppression
Measure Participants	53	54
Number [participants]	3 5.6%	1 1.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paricalcitol, Calcitriol
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	On the basis of prior published reports, we estimated a 5% rate of hypercalcemia with paricalcitol and a 30% rate with calcitriol. To have a 90% power to detect a difference at the P=0.05 confidence level, 42 patients per group were needed. Assuming a 30% dropout rate over the course of the study, we planned to randomize 110 patients.
Statistical Test of Hypothesis	p-Value	0.36
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Arm/Group Title	Paricalcitol		Calcitriol
Arm/Group Description	titrated to achieve 40-60% PTH suppression Paricalcitol: 1 mcg daily, adjusted to achieve 40-60% PTH suppression		titrated to achieve 40-60% PTH suppression Calcitriol: 0.25 mcg daily, adjusted to achieve 40-60% PTH suppression
All Cause Mortality
	Paricalcitol		Calcitriol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Paricalcitol		Calcitriol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		1/54 (1.9%)
Endocrine disorders
Hypercalcemia	0/53 (0%)	0	1/54 (1.9%)	1
Other (Not Including Serious) Adverse Events
	Paricalcitol		Calcitriol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/53 (28.3%)		12/54 (22.2%)
Musculoskeletal and connective tissue disorders
Musculoskeletal	15/53 (28.3%)	15	12/54 (22.2%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.