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

Hypertrophy, Left Ventricular Clinical Trial

— PRIMO II  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00616902
• Other study ID #: M10-221
• Secondary ID: 2007-005092-33
• Status: Terminated
• Phase: Phase 3
• First received: February 5, 2008
• Last updated: January 18, 2012
• Start date: January 2009
• Est. completion date: May 2009

Study information

• Verified date: January 2012
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Chronic Kidney Disease (CKD) Stage 5
• Hypertrophy
• Hypertrophy, Left Ventricular
• Kidney Diseases
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• paricalcitol injection 4 mcg/mL
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

Locations

Country	Name	City	State
Australia	Liverpool Hospital - Renal Unit	Liverpool	New South Wales
Australia	Royal Melbourne Hospital - Dept. of Nephrology	Parkville	Victoria
Australia	Westmead Hospital - Dept. of Renal Medicine	Sydney	New South Wales
Australia	The Princess Alexandra Hospital - Nephrology Dept.	Wooloongabba	Queensland
Czech Republic	Faculty Hospital Brno	Brno
Czech Republic	FN Pizen Lochotin - Charles University Teaching Hospital	Pizen
Czech Republic	IKEM - Nephrology Dept.	Prague 4
Czech Republic	1st LF UK - Nephrology Dept.	Praha 2
Czech Republic	1st LF UK - Nephrology Dept. Strahov	Praha 6
Germany	KfH Nierenzentrum	Coburg
Germany	Gemeinschaftspraxis Dialyse	Dortmund
Germany	Gemeinschaftspraxix Karlstrasse	Dusseldorf
Germany	Niren-, Dochdruck und Dialysepraxis	Nettetal
Greece	IASO General - Renal Unit	Athens
Greece	Papageorgiou General Hospital of Thessaloniki	Thessaloniki
Puerto Rico	Fresenius Medical Care	Caguas
Puerto Rico	University of Puerto Rico	Rio Piedras
Romania	Institut Clinic Fundeni - Clinica Medicine Interna/Nefrologie	Bucuresti
Romania	Spitalul "Dr. C. Davila" - Clinica de Nefrologie	Bucuresti
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	Iasi
Russian Federation	City Clinical Hospital #52	Moscow
Russian Federation	Hospital for War Veterans #2	Moscow
Russian Federation	Moscow City Clinical Hospital named after Botkin	Moscow
Spain	Servicio de Nefrologia - Planta Baja	Cordoba
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	Sevilla
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
United Kingdom	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 States	Western Nephrology and Metabolic bone disease	Arvada	Colorado
United States	FMC-NA Central Atlanta	Atlanta	Georgia
United States	National Institute of Clinical Research	Bakersfield	California
United States	Brookdale Physicians Dialysis Associates	Brooklyn	New York
United States	The University of Chicago - Stony Island Dialysis Unit	Chicago	Illinois
United States	University of Illinois at Chicago - Nephrology Research	Chicago	Illinois
United States	MetroHealth Medical Center	Cleveland	Ohio
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	Southwest Houston Research, Ltd	Houston	Texas
United States	Fresenius Medical Care	Kalamazoo	Michigan
United States	V.A. Medical Center Research	Kansas City	Missouri
United States	G. Edward Newman, MD, LLC	Knoxville	Tennessee
United States	National Institute of Clinical Research	Los Angeles	California
United States	University of Southern California Kidney Center	Los Angeles	California
United States	V.A. Tennessee Valley Healthcare System	Nashville	Tennessee
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Arizona Kidney Disease & Hypertension Center	Phoenix	Arizona
United States	Biolab Research LLC	Rockville	Maryland
United States	The University of Texas - Health Science Center at San Antonio	San Antonio	Texas
United States	North American Research Institute - California Kidney Specialist	San Dimas	California
United States	Kidney Center of Simi Valley	Simi Valley	California
United States	Washington University School of Medicine - Division of Renal Disease	St. Louis	Missouri
United States	Fresenius Dialysis - Carrollwood	Tampa	Florida
United States	Southwest Kidney Institute	Tempe	Arizona
United States	Washington Nephrology Associates, LLP	Washington	District of Columbia
United States	Western Nephrology	Westminster	Colorado
United States	Nephrology Associates, PLLC	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Abbott	Harvard University, Massachusetts General Hospital

Countries where clinical trial is conducted

United States,  Australia,  Czech Republic,  Germany,  Greece,  Italy,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Left Ventricular Mass Index (LVMI) Over 48 Weeks Measured by Cardiac Magnetic Resonance Imaging (MRI)	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.	Baseline, 24 Weeks, and 48 Weeks/Early Termination	No
Secondary	Change From Baseline in the Echocardiographic Assessment of Diastolic Function Assessed by Evaluating Changes in Diastolic Mitral Annular Relaxation Velocity (E') Over 48 Weeks.	Mitral Annular relaxation velocity is a measure of diastolic heart function.	Baseline, 24 Weeks, and 48 Weeks/Early Termination	No
Secondary	Change From Baseline in Evaluating Changes in the Additional Measure of Diastolic Function of Isovolumetric Relaxation Time (IVRT) Over 48 Weeks.	Isovolumetric relaxation time is a measure of diastolic heart function.	Baseline, 24 Weeks, and 48 Weeks/Early Termination	No
Secondary	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.	The ratio of peak E-wave velocity to lateral e-wave velocity is a measure of diastolic heart function.	Baseline, Week 24, and Week 48/Early Termination	No
Secondary	Change From Baseline in Evaluating Changes in the Additional Measure of Diastolic Function E-wave Deceleration Time (DT) Over 48 Weeks	E-wave deceleration time is a measure of diastolic heart function.	Baseline, 24 Weeks, and 48 Weeks/Early Termination	No
Secondary	Change From Baseline in Biological Marker Triiodothyronine (T3).	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.	Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)	No
Secondary	Change From Baseline in Biological Marker Plasma Troponin-T Over 48 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.	Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)	No
Secondary	Change From Baseline in Biological Marker Plasma Interleukin-6 (IL-6) Over 48 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.	Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)	No
Secondary	Change From Baseline in Biological Marker Plasma High Sensitivity C-reactive Protein (hsCRP) Over 48 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.	Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)	No
Secondary	Change From Baseline in Biological Marker Plasma B-Type Natriuretic Peptide (BNP)	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.	Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)	No