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The PRIMO II Study: Paricalcitol Injection Benefits in Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease (CKD) Stage 5

This study has been terminated.
(This study was prematurely terminated due to low enrollment)
Sponsor:
Collaborators:
Massachusetts General Hospital
Harvard University
Information provided by (Responsible Party):
Abbott
ClinicalTrials.gov Identifier:
NCT00616902
First received: February 5, 2008
Last updated: January 18, 2012
Last verified: January 2012

February 5, 2008
January 18, 2012
January 2009
May 2009   (final data collection date for primary outcome measure)
Change From Baseline in Left Ventricular Mass Index (LVMI) Over 48 Weeks Measured by Cardiac Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline, 24 Weeks, and 48 Weeks/Early Termination ] [ Designated as safety issue: No ]

Change from Baseline in left ventricular mass index (LVMI) over 48 weeks measured by cardiac MRI. The effects of paricalcitol injection on progression or regression of left ventricular hypertrophy (LVH) in participants with Stage 5 chronic kidney disease (CKD) on hemodialysis (HD) compared to placebo. Left Ventricular Mass is normalized to the participant's height by the following equation to obtain LVMI: LVM (g) divided by height (m)2.7.

The primary comparison was between the 4 mcg paricalcitol injection and the placebo treatment groups in the change from baseline to Week 48.

Identify LV Mass Index (LVMI) changes by comparing sequential cardiac magnetic resonance imaging (MRI). [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00616902 on ClinicalTrials.gov Archive Site
  • Change From Baseline in the Echocardiographic Assessment of Diastolic Function Assessed by Evaluating Changes in Diastolic Mitral Annular Relaxation Velocity (E') Over 48 Weeks. [ Time Frame: Baseline, 24 Weeks, and 48 Weeks/Early Termination ] [ Designated as safety issue: No ]
    Mitral Annular relaxation velocity is a measure of diastolic heart function.
  • Change From Baseline in Evaluating Changes in the Additional Measure of Diastolic Function of Isovolumetric Relaxation Time (IVRT) Over 48 Weeks. [ Time Frame: Baseline, 24 Weeks, and 48 Weeks/Early Termination ] [ Designated as safety issue: No ]
    Isovolumetric relaxation time is a measure of diastolic heart function.
  • Change From Baseline in Evaluating Changes in the Additional Measure of Diastolic Function of Peak E-wave Velocity to Lateral E-wave Velocity (E/E') Over 48 Weeks. [ Time Frame: Baseline, Week 24, and Week 48/Early Termination ] [ Designated as safety issue: No ]
    The ratio of peak E-wave velocity to lateral e-wave velocity is a measure of diastolic heart function.
  • Change From Baseline in Evaluating Changes in the Additional Measure of Diastolic Function E-wave Deceleration Time (DT) Over 48 Weeks [ Time Frame: Baseline, 24 Weeks, and 48 Weeks/Early Termination ] [ Designated as safety issue: No ]
    E-wave deceleration time is a measure of diastolic heart function.
  • Change From Baseline in Biological Marker Triiodothyronine (T3). [ Time Frame: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks) ] [ Designated as safety issue: No ]
    Plasma T3 is a circulating hormone that may have an effect on diastolic heart function and its level may be affected by treatment with paricalcitol. The study was terminated early (prior to any subject reaching Week 24). The values are for Baseline and Early Termination only. Each of the 12 randomized subjects terminated at different study weeks; therefore Early Termination cannot be defined as a specific week and varies for different subjects. Of the 12 subjects, 11 had early termination visits and 1 didn't. The final visit week range is 4-16.
  • Change From Baseline in Biological Marker Plasma Troponin-T Over 48 Weeks [ Time Frame: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks) ] [ Designated as safety issue: No ]
    Plasma troponin-t is a marker of heart damage and and its level may be affected by treatment with paricalcitol. The study was terminated early (prior to any subject reaching Week 24). The values are for Baseline and Early Termination only. Each of the 12 randomized subjects terminated at different study weeks; therefore Early Termination cannot be defined as a specific week and varies for different subjects. Of the 12 subjects, 11 had early termination visits and 1 didn't. The final visit week range is 4-16.
  • Change From Baseline in Biological Marker Plasma Interleukin-6 (IL-6) Over 48 Weeks [ Time Frame: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks) ] [ Designated as safety issue: No ]
    Plasma IL-6 is a biomarker of inflammation that may have an effect on heart function and its level may be affected by treatment with paricalcitol. The study was terminated early (prior to any subject reaching Week 24). The values are for Baseline and Early Termination only. Each of the 12 randomized subjects terminated at different study weeks; therefore Early Termination cannot be defined as a specific week and varies for different subjects. Of the 12 subjects, 11 had early termination visits and 1 didn't. The final visit week range is 4-16.
  • Change From Baseline in Biological Marker Plasma High Sensitivity C-reactive Protein (hsCRP) Over 48 Weeks [ Time Frame: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks) ] [ Designated as safety issue: No ]
    Plasma high sensitivity CRP is a biomarker of inflammation that may have an effect on heart function and its level may be affected by treatment with paricalcitol. The study was terminated early (prior to any subject reaching Week 24). The values are for Baseline and Early Termination only. Each of the 12 randomized subjects terminated at different study weeks; therefore Early Termination cannot be defined as a specific week and varies for different subjects. Of the 12 subjects, 11 had early termination visits and 1 didn't. The final visit week range is 4-16.
  • Change From Baseline in Biological Marker Plasma B-Type Natriuretic Peptide (BNP) [ Time Frame: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks) ] [ Designated as safety issue: No ]
    Plasma BNP is a product from the heart that becomes elevated with an enlarged heart and its level may be affected by treatment with paricalcitol. The study was terminated early (prior to any subject reaching Week 24). The values are for Baseline and Early Termination only. Each of the 12 randomized subjects terminated at different study weeks; therefore Early Termination cannot be defined as a specific week and varies for different subjects. Of the 12 subjects, 11 had early termination visits and 1 didn't. The final visit week range is 4-16.
  • Change in diastolic function by comparing changes in various measures of diastolic function (IVRT, E/E', DT), including diastolic mitral annular relaxation velocity. [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Changes in biological and inflammatory markers that have been linked to CVD in CKD subjects, by comparing static results over time. Markers to be evaluated are: T3, IL-6, troponin-T, BNP, and hsCRP [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
The PRIMO II Study: Paricalcitol Injection Benefits in Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease (CKD) Stage 5
Clinical Study Protocol M10-221 The PRIMO II Study: Paricalcitol Injection Benefits in Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease (CKD) Stage 5

To evaluate the effects of paricalcitol injection on cardiac structure and function over 48 weeks in subjects with Stage 5 Chronic Kidney Disease (CKD) receiving hemodialysis who have left ventricular hypertrophy (LVH).

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Chronic Kidney Disease (CKD) Stage 5
  • Hypertrophy, Left Ventricular
  • Drug: paricalcitol injection 4 mcg/mL
    Paricalcitol Injection 4 mcg/mL intravenously three times a week during dialysis
    Other Names:
    • ABT-358
    • paricalcitol
    • Zemplar
  • Drug: Placebo Injection 4 mcg/mL
    Placebo Injection 4 mcg/mL given intravenously three times a week during dialysis
    Other Name: placebo
  • Active Comparator: Paricalcitol Injection 4 mcg/mL
    Paricalcitol Injection 4 mcg/mL given intravenously 3 times per week during dialysis
    Intervention: Drug: paricalcitol injection 4 mcg/mL
  • Placebo Comparator: Placebo Injection 4 mcg/mL
    Placebo Injection 4 mcg/mL given intravenously three times a week during dialysis
    Intervention: Drug: Placebo Injection 4 mcg/mL
Thadhani R. Targeted ablation of the vitamin D 1alpha-hydroxylase gene: getting to the heart of the matter. Kidney Int. 2008 Jul;74(2):141-3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
12
May 2009
May 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Stage 5 CKD receiving chronic hemodialysis three times per week for >= 3 months and <= 12 months from date of Randomization (Day 1).
  • Serum intact parathyroid hormone (iPTH) value between 100-350 pg/mL.
  • Serum calcium level between 8.4-10.5 mg/dL (2.1-2.6 mmol/L).
  • Phosphate < 7 mg/dL.
  • Serum albumin >= 3.0 g/dL (30 g/L).
  • Echocardiogram results:

    • For females, left ventricular (LV) ejection fraction >= 50% and septal wall thickness between 11-17 mm.
    • For males, LV ejection fraction >= 50% and septal wall thickness between 12-18 mm.
  • If the subject is receiving Renin Angiotensin-Aldosterone System (RAAS) inhibitors, the dose must have been stable for greater than one month prior to the Screening Period.
  • A technically adequate baseline cardiac magnetic resonance imaging (MRI).
  • If female, subject is not breast feeding or is not pregnant, or is not of childbearing potential, defined as postmenopausal for at least one year or surgically sterile, or is of childbearing potential and practicing one of the following methods of birth control:
  • Double-barrier method
  • Hormonal contraceptives for at least three months prior to and during study drug administration
  • Maintains a monogamous relationship with a vasectomized partner
  • Total abstinence from sexual intercourse during the study.

Exclusion Criteria:

  • Subject has previously been on active vitamin D therapy (calcitriol, paricalcitol, doxercalciferol, alfacalcidol) for a total duration greater than three months since the start of dialysis.
  • Subject has a history of an allergic reaction or significant sensitivity to paricalcitol or to drugs similar to the study drug.
  • Subject is expected to receive an increased dose of RAAS inhibitor (Angiotensin converting enzyme inhibitor [ACEi], Angiotensin II receptor blocker [ARB] or aldosterone inhibitor) during the course of the study.
  • Subject has clinically significant coronary artery disease (CAD) within 3 months prior to the Screening Period, defined as one of the following:

    • Hospitalization for myocardial infarction (MI) or unstable angina; or
    • New onset angina with positive functional study or coronary angiogram revealing stenosis; or
    • Coronary revascularization procedure.
  • Subject has major cardiac valve abnormality linked with left ventricular hypertrophy (LVH) and/or diastolic dysfunction, defined as one of the following:

    • Aortic valve area <= 1.5 cm2 or a mean gradient of > 20 mmHg; or
    • Regurgitation lesions; more than moderate mitral regurgitation or more than moderate aortic regurgitation.
  • Subject has asymmetric septal hypertrophy.
  • Subject has had a severe cerebrovascular accident (CVA) within the last three months (e.g., hemorrhagic) prior to screening.
  • Full remission from a malignancy for less than one year except completely excised non-Melanoma skin cancer (e.g. basal or squamous carcinoma) or any history of bone metastasis.
  • Subject has co-morbid conditions.
  • Subject has received any investigational drug within 30 days prior to study drug administration or is currently enrolled in another clinical trial.
  • Subject has poorly controlled hypertension.
  • Subject has history of renal artery stenosis, primary aldosteronism or pheochromocytoma
  • Subject is taking calcitonin, bisphosphonates, cinacalcet, glucocorticoids (except topical or inhaled glucocorticoids)
  • Subject is currently receiving immunosuppressant therapy and/or high doses of glucocorticoids
  • Subject is known to be HIV positive.
  • Use of known inhibitors or inducers of cytochrome P450 3A (CYP3A) within two weeks prior to study drug administration
  • Subject is contraindicated for the MRI examination
  • Investigator considers subject unsuitable for any reason
  • Subject has a history of drug or alcohol abuse within six months prior to screening
  • Subject weighs more than 340 pounds (154 kg)
  • Subject has had a liver transplant
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Czech Republic,   Germany,   Greece,   Italy,   Poland,   Puerto Rico,   Romania,   Russian Federation,   Spain,   Taiwan,   United Kingdom
 
NCT00616902
M10-221, 2007-005092-33
Yes
Abbott
Abbott
  • Massachusetts General Hospital
  • Harvard University
Study Director: Dennis Andress, MD Abbott
Abbott
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP