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
  Purpose

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).


Condition Intervention Phase
Chronic Kidney Disease (CKD) Stage 5
Hypertrophy, Left Ventricular
Drug: paricalcitol injection 4 mcg/mL
Drug: Placebo Injection 4 mcg/mL
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Abbott:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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.


Enrollment: 12
Study Start Date: January 2009
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Paricalcitol Injection 4 mcg/mL
Paricalcitol Injection 4 mcg/mL given intravenously 3 times per week during dialysis
Drug: paricalcitol injection 4 mcg/mL
Paricalcitol Injection 4 mcg/mL intravenously three times a week during dialysis
Other Names:
  • ABT-358
  • paricalcitol
  • Zemplar
Placebo Comparator: Placebo Injection 4 mcg/mL
Placebo Injection 4 mcg/mL given intravenously three times a week during dialysis
Drug: Placebo Injection 4 mcg/mL
Placebo Injection 4 mcg/mL given intravenously three times a week during dialysis
Other Name: placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00616902

  Hide Study Locations
Locations
United States, Arizona
Arizona Kidney Disease & Hypertension Center
Phoenix, Arizona, United States, 85027
Southwest Kidney Institute
Tempe, Arizona, United States, 85284
United States, California
National Institute of Clinical Research
Bakersfield, California, United States, 93309
National Institute of Clinical Research
Los Angeles, California, United States, 90017
University of Southern California Kidney Center
Los Angeles, California, United States, 90033
North American Research Institute - California Kidney Specialist
San Dimas, California, United States, 91773
Kidney Center of Simi Valley
Simi Valley, California, United States, 93065
United States, Colorado
Western Nephrology and Metabolic bone disease
Arvada, Colorado, United States, 80002
Western Nephrology
Westminster, Colorado, United States, 80031
United States, District of Columbia
Washington Nephrology Associates, LLP
Washington, District of Columbia, United States, 20017
United States, Florida
Fresenius Dialysis - Carrollwood
Tampa, Florida, United States, 33624
United States, Georgia
FMC-NA Central Atlanta
Atlanta, Georgia, United States, 30329
United States, Illinois
The University of Chicago - Stony Island Dialysis Unit
Chicago, Illinois, United States, 60617
University of Illinois at Chicago - Nephrology Research
Chicago, Illinois, United States, 60612
Evanston Northwestern Healthcare Corp. - Division of Nephrology
Evanston, Illinois, United States, 60201
Research By Design, LLC
Evergreen Park, Illinois, United States, 60805
North Suburban Nephrology
Gurnee, Illinois, United States, 60031
United States, Maryland
Biolab Research LLC
Rockville, Maryland, United States, 20852
United States, Michigan
Fresenius Medical Care
Kalamazoo, Michigan, United States, 49007
United States, Missouri
V.A. Medical Center Research
Kansas City, Missouri, United States, 64128
Washington University School of Medicine - Division of Renal Disease
St. Louis, Missouri, United States, 63110
United States, Nebraska
Creighton University Medical Center
Omaha, Nebraska, United States, 68131
United States, New York
Brookdale Physicians Dialysis Associates
Brooklyn, New York, United States, 11212
United States, North Carolina
Nephrology Associates, PLLC
Winston-Salem, North Carolina, United States, 27103-7108
United States, Ohio
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
United States, Tennessee
G. Edward Newman, MD, LLC
Knoxville, Tennessee, United States, 37923
V.A. Tennessee Valley Healthcare System
Nashville, Tennessee, United States, 37212
United States, Texas
Southwest Houston Research, Ltd
Houston, Texas, United States, 77099
The University of Texas - Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
Australia, New South Wales
Liverpool Hospital - Renal Unit
Liverpool, New South Wales, Australia, 2170
Westmead Hospital - Dept. of Renal Medicine
Sydney, New South Wales, Australia, 2145
Australia, Queensland
The Princess Alexandra Hospital - Nephrology Dept.
Wooloongabba, Queensland, Australia, 4102
Australia, Victoria
Royal Melbourne Hospital - Dept. of Nephrology
Parkville, Victoria, Australia, 3050
Czech Republic
Faculty Hospital Brno
Brno, Czech Republic, 62500
FN Pizen Lochotin - Charles University Teaching Hospital
Pizen, Czech Republic, 304 60
IKEM - Nephrology Dept.
Prague 4, Czech Republic, 140 21
1st LF UK - Nephrology Dept.
Praha 2, Czech Republic, 120 08
1st LF UK - Nephrology Dept. Strahov
Praha 6, Czech Republic, 169 00
Germany
KfH Nierenzentrum
Coburg, Germany, 96450
Gemeinschaftspraxis Dialyse
Dortmund, Germany, 44263
Gemeinschaftspraxix Karlstrasse
Dusseldorf, Germany, 40210
Niren-, Dochdruck und Dialysepraxis
Nettetal, Germany, 41334
Wurzburg, Germany, 97080
Greece
IASO General - Renal Unit
Athens, Greece, 15562
Papageorgiou General Hospital of Thessaloniki
Thessaloniki, Greece, 56403
Italy
Bologna, Italy, 40138
Monza, Italy, 20052
Pavia, Italy, 27100
Trieste, Italy, 34125
Poland
Katowice, Poland, 40-027
Lodz, Poland, 90-153
Szczecin, Poland, 70-111
Warszawa, Poland, 02-507
Warszawa, Poland, 02-006
Puerto Rico
Fresenius Medical Care
Caguas, Puerto Rico, 00725
University of Puerto Rico
Rio Piedras, Puerto Rico, 00935
Romania
Institut Clinic Fundeni - Clinica Medicine Interna/Nefrologie
Bucuresti, Romania, 022328
Spitalul "Dr. C. Davila" - Clinica de Nefrologie
Bucuresti, Romania, 013221
Nefromed Dialysis Centre Cluj
Cluj-Napoca, Romania, 400006
Spitalul Clinic Judetean Cluj - Clinica de Nefrologie
Cluj-Napoca, Romania, 400006
Spitalul Clinic "Dr. C. I. Parhon" - Clinica de Nefrologie
Iasi, Romania, 700503
Russian Federation
City Clinical Hospital #52
Moscow, Russian Federation, 123182
Hospital for War Veterans #2
Moscow, Russian Federation, 127473
Moscow City Clinical Hospital named after Botkin
Moscow, Russian Federation, 125284
Spain
Servicio de Nefrologia - Planta Baja
Cordoba, Spain, 14004
Fundacion Jimenez Diaz - Servicio de Nefrologia
Madrid, Spain, 28040
Hospital Universitario Son Dureta
Palma de Mallorca, Spain, 07014
Clinica Universitaria de la Universidad de Navarra
Pamplona, Spain, 31008
Hospital Universitario Virgen del Rocio - Servicio de Nefrologia
Sevilla, Spain, 41013
Taiwan
Hsin-Jen Hospital
Hsin-Chuang City, Taiwan
Cheng Hsin Rehabilitation Medical Center
Taipei, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Chang Gung Memorial Hospital
Taoyuan, Taiwan
United Kingdom
University Hospitals Coventry and Warwickshire NHS Trust - University Hospital (UHCW)
Coventry, United Kingdom, CV2 2DX
Hammersmith Hospital
London, United Kingdom, W12 0NN
Salford Royal NHS Foundation Trust - Dept. of Nephrology
Salford, United Kingdom, M6 8HD
Sponsors and Collaborators
Abbott
Massachusetts General Hospital
Harvard University
Investigators
Study Director: Dennis Andress, MD Abbott
  More Information

No publications provided by Abbott

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Abbott
ClinicalTrials.gov Identifier: NCT00616902     History of Changes
Other Study ID Numbers: M10-221, 2007-005092-33
Study First Received: February 5, 2008
Results First Received: May 21, 2010
Last Updated: January 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Abbott:
Zemplar, paricalcitol, PRIMO II

Additional relevant MeSH terms:
Hypertrophy
Hypertrophy, Left Ventricular
Kidney Diseases
Renal Insufficiency
Renal Insufficiency, Chronic
Cardiomegaly
Cardiovascular Diseases
Heart Diseases
Pathological Conditions, Anatomical
Urologic Diseases
Ergocalciferols
Bone Density Conservation Agents
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Vitamins

ClinicalTrials.gov processed this record on October 20, 2014