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

NCT ID: NCT00616902

Last Updated: 2012-01-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2009-05-31

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).

Conditions

Chronic Kidney Disease (CKD) Stage 5; Hypertrophy, Left Ventricular

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Paricalcitol Injection 4 mcg/mL

Paricalcitol Injection 4 mcg/mL given intravenously 3 times per week during dialysis

Group Type: ACTIVE_COMPARATOR

paricalcitol injection 4 mcg/mL

Intervention Type: DRUG

Paricalcitol Injection 4 mcg/mL intravenously three times a week during dialysis

Placebo Injection 4 mcg/mL

Placebo Injection 4 mcg/mL given intravenously three times a week during dialysis

Group Type: PLACEBO_COMPARATOR

Placebo Injection 4 mcg/mL

Intervention Type: DRUG

Placebo Injection 4 mcg/mL given intravenously three times a week during dialysis

Interventions

paricalcitol injection 4 mcg/mL

Paricalcitol Injection 4 mcg/mL intravenously three times a week during dialysis

Intervention Type: DRUG

Placebo Injection 4 mcg/mL

Placebo Injection 4 mcg/mL given intravenously three times a week during dialysis

Intervention Type: DRUG

Other Intervention Names

ABT-358; paricalcitol; Zemplar; placebo

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Harvard University

OTHER

Sponsor Role: collaborator

Abbott

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dennis Andress, MD

Role: STUDY_DIRECTOR

Abbott

Locations

Arizona Kidney Disease & Hypertension Center

Phoenix, Arizona, United States

Southwest Kidney Institute

Tempe, Arizona, United States

National Institute of Clinical Research

Bakersfield, California, United States

National Institute of Clinical Research

Los Angeles, California, United States

University of Southern California Kidney Center

Los Angeles, California, United States

North American Research Institute - California Kidney Specialist

San Dimas, California, United States

Kidney Center of Simi Valley

Simi Valley, California, United States

Western Nephrology and Metabolic bone disease

Arvada, Colorado, United States

Western Nephrology

Westminster, Colorado, United States

Washington Nephrology Associates, LLP

Washington D.C., District of Columbia, United States

Fresenius Dialysis - Carrollwood

Tampa, Florida, United States

FMC-NA Central Atlanta

Atlanta, Georgia, United States

University of Illinois at Chicago - Nephrology Research

Chicago, Illinois, United States

The University of Chicago - Stony Island Dialysis Unit

Chicago, Illinois, United States

Evanston Northwestern Healthcare Corp. - Division of Nephrology

Evanston, Illinois, United States

Research By Design, LLC

Evergreen Park, Illinois, United States

North Suburban Nephrology

Gurnee, Illinois, United States

Biolab Research LLC

Rockville, Maryland, United States

Fresenius Medical Care

Kalamazoo, Michigan, United States

V.A. Medical Center Research

Kansas City, Missouri, United States

Washington University School of Medicine - Division of Renal Disease

St Louis, Missouri, United States

Creighton University Medical Center

Omaha, Nebraska, United States

Brookdale Physicians Dialysis Associates

Brooklyn, New York, United States

Nephrology Associates, PLLC

Winston-Salem, North Carolina, United States

MetroHealth Medical Center

Cleveland, Ohio, United States

G. Edward Newman, MD, LLC

Knoxville, Tennessee, United States

V.A. Tennessee Valley Healthcare System

Nashville, Tennessee, United States

Southwest Houston Research, Ltd

Houston, Texas, United States

The University of Texas - Health Science Center at San Antonio

San Antonio, Texas, United States

Liverpool Hospital - Renal Unit

Liverpool, New South Wales, Australia

Westmead Hospital - Dept. of Renal Medicine

Sydney, New South Wales, Australia

The Princess Alexandra Hospital - Nephrology Dept.

Wooloongabba, Queensland, Australia

Royal Melbourne Hospital - Dept. of Nephrology

Parkville, Victoria, Australia

Faculty Hospital Brno

Brno, , Czechia

FN Pizen Lochotin - Charles University Teaching Hospital

Pizen, , Czechia

1st LF UK - Nephrology Dept.

Prague, , Czechia

IKEM - Nephrology Dept.

Prague, , Czechia

1st LF UK - Nephrology Dept. Strahov

Prague, , Czechia

KfH Nierenzentrum

Coburg, , Germany

Gemeinschaftspraxis Dialyse

Dortmund, , Germany

Gemeinschaftspraxix Karlstrasse

Düsseldorf, , Germany

Niren-, Dochdruck und Dialysepraxis

Nettetal, , Germany

Würzburg, , Germany

IASO General - Renal Unit

Athens, , Greece

Papageorgiou General Hospital of Thessaloniki

Thessaloniki, , Greece

Bologna, , Italy

Monza, , Italy

Pavia, , Italy

Trieste, , Italy

Katowice, , Poland

Lodz, , Poland

Szczecin, , Poland

Warsaw, , Poland

Warsaw, , Poland

Fresenius Medical Care

Caguas, , Puerto Rico

University of Puerto Rico

Rio Piedras, , Puerto Rico

Spitalul "Dr. C. Davila" - Clinica de Nefrologie

Bucharest, , Romania

Institut Clinic Fundeni - Clinica Medicine Interna/Nefrologie

Bucharest, , Romania

Nefromed Dialysis Centre Cluj

Cluj-Napoca, , Romania

Spitalul Clinic Judetean Cluj - Clinica de Nefrologie

Cluj-Napoca, , Romania

Spitalul Clinic "Dr. C. I. Parhon" - Clinica de Nefrologie

Iași, , Romania

City Clinical Hospital #52

Moscow, , Russia

Moscow City Clinical Hospital named after Botkin

Moscow, , Russia

Hospital for War Veterans #2

Moscow, , Russia

Servicio de Nefrologia - Planta Baja

Córdoba, , Spain

Fundacion Jimenez Diaz - Servicio de Nefrologia

Madrid, , Spain

Hospital Universitario Son Dureta

Palma de Mallorca, , Spain

Clinica Universitaria de la Universidad de Navarra

Pamplona, , Spain

Hospital Universitario Virgen del Rocio - Servicio de Nefrologia

Seville, , Spain

Cheng Hsin Rehabilitation Medical Center

Taipei, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Hsin-Jen Hospital

Xinzhuang, , Taiwan

University Hospitals Coventry and Warwickshire NHS Trust - University Hospital (UHCW)

Coventry, , United Kingdom

Hammersmith Hospital

London, , United Kingdom

Salford Royal NHS Foundation Trust - Dept. of Nephrology

Salford, , United Kingdom

Countries

United States; Australia; Czechia; Germany; Greece; Italy; Poland; Puerto Rico; Romania; Russia; Spain; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 18591942 (View on PubMed)

Other Identifiers

2007-005092-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M10-221

Identifier Type: -

Identifier Source: org_study_id