Clinical trial NCT00616902: The PRIMO II Study: Paricalcitol Injection Benefits in Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease (CKD) Stage 5
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Kidney Disease (CKD) Stage 5
Hypertrophy, Left Ventricular
Keywords: Zemplar, paricalcitol, PRIMO II
Lead sponsor: Abbott
Sponsor class: INDUSTRY
Collaborators: name: Massachusetts General Hospital
name: Harvard University
First posted: 2008-02-15
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: Change From Baseline in Left Ventricular Mass Index (LVMI) Over 48 Weeks Measured by Cardiac Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, 24 Weeks, and 48 Weeks/Early Termination
Secondary outcomes:
measure: Change From Baseline in the Echocardiographic Assessment of Diastolic Function Assessed by Evaluating Changes in Diastolic Mitral Annular Relaxation Velocity (E') Over 48 Weeks.
timeFrame: Baseline, 24 Weeks, and 48 Weeks/Early Termination
measure: Change From Baseline in Evaluating Changes in the Additional Measure of Diastolic Function of Isovolumetric Relaxation Time (IVRT) Over 48 Weeks.
timeFrame: Baseline, 24 Weeks, and 48 Weeks/Early Termination
measure: 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.
timeFrame: Baseline, Week 24, and Week 48/Early Termination
measure: Change From Baseline in Evaluating Changes in the Additional Measure of Diastolic Function E-wave Deceleration Time (DT) Over 48 Weeks
timeFrame: Baseline, 24 Weeks, and 48 Weeks/Early Termination
measure: Change From Baseline in Biological Marker Triiodothyronine (T3).
timeFrame: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)
measure: Change From Baseline in Biological Marker Plasma Troponin-T Over 48 Weeks
timeFrame: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)
measure: Change From Baseline in Biological Marker Plasma Interleukin-6 (IL-6) Over 48 Weeks
timeFrame: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)
measure: Change From Baseline in Biological Marker Plasma High Sensitivity C-reactive Protein (hsCRP) Over 48 Weeks
timeFrame: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)
measure: Change From Baseline in Biological Marker Plasma B-Type Natriuretic Peptide (BNP)
timeFrame: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Kidney Disease & Hypertension Center
state: Arizona
city: Tempe
country: United States
facility: Southwest Kidney Institute
state: Arizona
city: Bakersfield
country: United States
facility: National Institute of Clinical Research
state: California
city: Los Angeles
country: United States
facility: National Institute of Clinical Research
state: California
city: Los Angeles
country: United States
facility: University of Southern California Kidney Center
state: California
city: San Dimas
country: United States
facility: North American Research Institute - California Kidney Specialist
state: California
city: Simi Valley
country: United States
facility: Kidney Center of Simi Valley
state: California
city: Arvada
country: United States
facility: Western Nephrology and Metabolic bone disease
state: Colorado
city: Westminster
country: United States
facility: Western Nephrology
state: Colorado
city: Washington
country: United States
facility: Washington Nephrology Associates, LLP
state: District of Columbia
city: Tampa
country: United States
facility: Fresenius Dialysis - Carrollwood
state: Florida
city: Atlanta
country: United States
facility: FMC-NA Central Atlanta
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago - Nephrology Research
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago - Stony Island Dialysis Unit
state: Illinois
city: Evanston
country: United States
facility: Evanston Northwestern Healthcare Corp. - Division of Nephrology
state: Illinois
city: Evergreen Park
country: United States
facility: Research By Design, LLC
state: Illinois
city: Gurnee
country: United States
facility: North Suburban Nephrology
state: Illinois
city: Rockville
country: United States
facility: Biolab Research LLC
state: Maryland
city: Kalamazoo
country: United States
facility: Fresenius Medical Care
state: Michigan
city: Kansas City
country: United States
facility: V.A. Medical Center Research
state: Missouri
city: St. Louis
country: United States
facility: Washington University School of Medicine - Division of Renal Disease
state: Missouri
city: Omaha
country: United States
facility: Creighton University Medical Center
state: Nebraska
city: Brooklyn
country: United States
facility: Brookdale Physicians Dialysis Associates
state: New York
city: Winston-Salem
country: United States
facility: Nephrology Associates, PLLC
state: North Carolina
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Knoxville
country: United States
facility: G. Edward Newman, MD, LLC
state: Tennessee
city: Nashville
country: United States
facility: V.A. Tennessee Valley Healthcare System
state: Tennessee
city: Houston
country: United States
facility: Southwest Houston Research, Ltd
state: Texas
city: San Antonio
country: United States
facility: The University of Texas - Health Science Center at San Antonio
state: Texas
city: Liverpool
country: Australia
facility: Liverpool Hospital - Renal Unit
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital - Dept. of Renal Medicine
state: New South Wales
city: Wooloongabba
country: Australia
facility: The Princess Alexandra Hospital - Nephrology Dept.
state: Queensland
city: Parkville
country: Australia
facility: Royal Melbourne Hospital - Dept. of Nephrology
state: Victoria
city: Brno
country: Czech Republic
facility: Faculty Hospital Brno
city: Pizen
country: Czech Republic
facility: FN Pizen Lochotin - Charles University Teaching Hospital
city: Prague 4
country: Czech Republic
facility: IKEM - Nephrology Dept.
city: Praha 2
country: Czech Republic
facility: 1st LF UK - Nephrology Dept.
city: Praha 6
country: Czech Republic
facility: 1st LF UK - Nephrology Dept. Strahov
city: Coburg
country: Germany
facility: KfH Nierenzentrum
city: Dortmund
country: Germany
facility: Gemeinschaftspraxis Dialyse
city: Dusseldorf
country: Germany
facility: Gemeinschaftspraxix Karlstrasse
city: Nettetal
country: Germany
facility: Niren-, Dochdruck und Dialysepraxis
city: Wurzburg
country: Germany
city: Athens
country: Greece
facility: IASO General - Renal Unit
city: Thessaloniki
country: Greece
facility: Papageorgiou General Hospital of Thessaloniki
city: Bologna
country: Italy
city: Monza
country: Italy
city: Pavia
country: Italy
city: Trieste
country: Italy
city: Katowice
country: Poland
city: Lodz
country: Poland
city: Szczecin
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Caguas
country: Puerto Rico
facility: Fresenius Medical Care
city: Rio Piedras
country: Puerto Rico
facility: University of Puerto Rico
city: Bucuresti
country: Romania
facility: Spitalul "Dr. C. Davila" - Clinica de Nefrologie
city: Bucuresti
country: Romania
facility: Institut Clinic Fundeni - Clinica Medicine Interna/Nefrologie
city: Cluj-Napoca
country: Romania
facility: Nefromed Dialysis Centre Cluj
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic Judetean Cluj - Clinica de Nefrologie
city: Iasi
country: Romania
facility: Spitalul Clinic "Dr. C. I. Parhon" - Clinica de Nefrologie
city: Moscow
country: Russian Federation
facility: City Clinical Hospital #52
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital named after Botkin
city: Moscow
country: Russian Federation
facility: Hospital for War Veterans #2
city: Cordoba
country: Spain
facility: Servicio de Nefrologia - Planta Baja
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz - Servicio de Nefrologia
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario Son Dureta
city: Pamplona
country: Spain
facility: Clinica Universitaria de la Universidad de Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio - Servicio de Nefrologia
city: Hsin-Chuang City
country: Taiwan
facility: Hsin-Jen Hospital
city: Taipei
country: Taiwan
facility: Cheng Hsin Rehabilitation Medical Center
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry and Warwickshire NHS Trust - University Hospital (UHCW)
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust - Dept. of Nephrology
Study officials:
affiliation: Abbott
name: Dennis Andress, MD
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1038/ki.2008.219.