The PRIMO II Study: Paricalcitol Injection Benefits in Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease (CKD) Stage 5
- Conditions
- Chronic Kidney Disease (CKD) Stage 5Hypertrophy, Left Ventricular
- Interventions
- Drug: paricalcitol injection 4 mcg/mLDrug: Placebo Injection 4 mcg/mL
- Registration Number
- NCT00616902
- Lead Sponsor
- Abbott
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 12
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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.
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Serum calcium level between 8.4-10.5 mg/dL (2.1-2.6 mmol/L).
-
Phosphate < 7 mg/dL.
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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.
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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.
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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
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Hormonal contraceptives for at least three months prior to and during study drug administration
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Maintains a monogamous relationship with a vasectomized partner
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Total abstinence from sexual intercourse during the study.
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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.
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Subject has a history of an allergic reaction or significant sensitivity to paricalcitol or to drugs similar to the study drug.
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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.
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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.
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Subject has had a severe cerebrovascular accident (CVA) within the last three months (e.g., hemorrhagic) prior to screening.
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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.
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Subject has co-morbid conditions.
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Subject has received any investigational drug within 30 days prior to study drug administration or is currently enrolled in another clinical trial.
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Subject has poorly controlled hypertension.
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Subject has history of renal artery stenosis, primary aldosteronism or pheochromocytoma
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Subject is taking calcitonin, bisphosphonates, cinacalcet, glucocorticoids (except topical or inhaled glucocorticoids)
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Subject is currently receiving immunosuppressant therapy and/or high doses of glucocorticoids
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Subject is known to be HIV positive.
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Use of known inhibitors or inducers of cytochrome P450 3A (CYP3A) within two weeks prior to study drug administration
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Subject is contraindicated for the MRI examination
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Investigator considers subject unsuitable for any reason
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Subject has a history of drug or alcohol abuse within six months prior to screening
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Subject weighs more than 340 pounds (154 kg)
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Subject has had a liver transplant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Paricalcitol Injection 4 mcg/mL paricalcitol injection 4 mcg/mL Paricalcitol Injection 4 mcg/mL given intravenously 3 times per week during dialysis Placebo Injection 4 mcg/mL Placebo Injection 4 mcg/mL Placebo Injection 4 mcg/mL given intravenously three times a week during dialysis
- Primary Outcome Measures
Name Time Method Change From Baseline in Left Ventricular Mass Index (LVMI) Over 48 Weeks Measured by Cardiac Magnetic Resonance Imaging (MRI) Baseline, 24 Weeks, and 48 Weeks/Early Termination 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in the Echocardiographic Assessment of Diastolic Function Assessed by Evaluating Changes in Diastolic Mitral Annular Relaxation Velocity (E') Over 48 Weeks. Baseline, 24 Weeks, and 48 Weeks/Early Termination 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. Baseline, 24 Weeks, and 48 Weeks/Early Termination 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. Baseline, Week 24, and Week 48/Early Termination 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 Baseline, 24 Weeks, and 48 Weeks/Early Termination E-wave deceleration time is a measure of diastolic heart function.
Change From Baseline in Biological Marker Triiodothyronine (T3). Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks) 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 Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks) 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 Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks) 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 Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks) 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) Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks) 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.
Trial Locations
- Locations (64)
North American Research Institute - California Kidney Specialist
🇺🇸San Dimas, California, United States
National Institute of Clinical Research
🇺🇸Los Angeles, California, United States
Southwest Kidney Institute
🇺🇸Tempe, Arizona, United States
Washington Nephrology Associates, LLP
🇺🇸Washington, District of Columbia, United States
FMC-NA Central Atlanta
🇺🇸Atlanta, Georgia, United States
Western Nephrology and Metabolic bone disease
🇺🇸Arvada, Colorado, United States
Western Nephrology
🇺🇸Westminster, Colorado, United States
University of Southern California Kidney Center
🇺🇸Los Angeles, California, United States
Gemeinschaftspraxix Karlstrasse
🇩🇪Dusseldorf, Germany
The University of Chicago - Stony Island Dialysis Unit
🇺🇸Chicago, Illinois, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Southwest Houston Research, Ltd
🇺🇸Houston, Texas, United States
IKEM - Nephrology Dept.
🇨🇿Prague 4, Czech Republic
Kidney Center of Simi Valley
🇺🇸Simi Valley, California, United States
North Suburban Nephrology
🇺🇸Gurnee, Illinois, United States
Biolab Research LLC
🇺🇸Rockville, Maryland, United States
Fresenius Medical Care
🇵🇷Caguas, Puerto Rico
Washington University School of Medicine - Division of Renal Disease
🇺🇸St. Louis, Missouri, United States
Brookdale Physicians Dialysis Associates
🇺🇸Brooklyn, New York, United States
Liverpool Hospital - Renal Unit
🇦🇺Liverpool, New South Wales, Australia
Royal Melbourne Hospital - Dept. of Nephrology
🇦🇺Parkville, Victoria, Australia
FN Pizen Lochotin - Charles University Teaching Hospital
🇨🇿Pizen, Czech Republic
The Princess Alexandra Hospital - Nephrology Dept.
🇦🇺Wooloongabba, Queensland, Australia
1st LF UK - Nephrology Dept.
🇨🇿Praha 2, Czech Republic
1st LF UK - Nephrology Dept. Strahov
🇨🇿Praha 6, Czech Republic
KfH Nierenzentrum
🇩🇪Coburg, Germany
Gemeinschaftspraxis Dialyse
🇩🇪Dortmund, Germany
Spitalul "Dr. C. Davila" - Clinica de Nefrologie
🇷🇴Bucuresti, Romania
Papageorgiou General Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
IASO General - Renal Unit
🇬🇷Athens, Greece
University of Puerto Rico
🇵🇷Rio Piedras, Puerto Rico
Institut Clinic Fundeni - Clinica Medicine Interna/Nefrologie
🇷🇴Bucuresti, Romania
Nefromed Dialysis Centre Cluj
🇷🇴Cluj-Napoca, Romania
City Clinical Hospital #52
🇷🇺Moscow, Russian Federation
Spitalul Clinic Judetean Cluj - Clinica de Nefrologie
🇷🇴Cluj-Napoca, Romania
Moscow City Clinical Hospital named after Botkin
🇷🇺Moscow, Russian Federation
Hospital for War Veterans #2
🇷🇺Moscow, Russian Federation
Spitalul Clinic "Dr. C. I. Parhon" - Clinica de Nefrologie
🇷🇴Iasi, Romania
Servicio de Nefrologia - Planta Baja
🇪🇸Cordoba, Spain
Clinica Universitaria de la Universidad de Navarra
🇪🇸Pamplona, Spain
Hospital Universitario Son Dureta
🇪🇸Palma de Mallorca, Spain
Hsin-Jen Hospital
🇨🇳Hsin-Chuang City, Taiwan
Hospital Universitario Virgen del Rocio - Servicio de Nefrologia
🇪🇸Sevilla, Spain
Cheng Hsin Rehabilitation Medical Center
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Hammersmith Hospital
🇬🇧London, United Kingdom
Westmead Hospital - Dept. of Renal Medicine
🇦🇺Sydney, New South Wales, Australia
G. Edward Newman, MD, LLC
🇺🇸Knoxville, Tennessee, United States
University of Illinois at Chicago - Nephrology Research
🇺🇸Chicago, Illinois, United States
Fundacion Jimenez Diaz - Servicio de Nefrologia
🇪🇸Madrid, Spain
University Hospitals Coventry and Warwickshire NHS Trust - University Hospital (UHCW)
🇬🇧Coventry, United Kingdom
Salford Royal NHS Foundation Trust - Dept. of Nephrology
🇬🇧Salford, United Kingdom
Research By Design, LLC
🇺🇸Evergreen Park, Illinois, United States
Evanston Northwestern Healthcare Corp. - Division of Nephrology
🇺🇸Evanston, Illinois, United States
Niren-, Dochdruck und Dialysepraxis
🇩🇪Nettetal, Germany
Faculty Hospital Brno
🇨🇿Brno, Czech Republic
Arizona Kidney Disease & Hypertension Center
🇺🇸Phoenix, Arizona, United States
Nephrology Associates, PLLC
🇺🇸Winston-Salem, North Carolina, United States
V.A. Tennessee Valley Healthcare System
🇺🇸Nashville, Tennessee, United States
The University of Texas - Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Fresenius Dialysis - Carrollwood
🇺🇸Tampa, Florida, United States
Creighton University Medical Center
🇺🇸Omaha, Nebraska, United States
V.A. Medical Center Research
🇺🇸Kansas City, Missouri, United States