The PRIMO Study: Paricalcitol Capsules Benefits Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease Stage 3/4

Chronic Kidney Disease Clinical Trial

— PRIMO  

Official title:

The PRIMO Study: Paricalcitol Capsules Benefits in Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease Stage 3/4

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00497146
• Other study ID #: M10-030
• Secondary ID: 2007-001689-34
• Status: Completed
• Phase: Phase 3
• First received: July 3, 2007
• Last updated: March 8, 2013
• Start date: February 2008
• Est. completion date: March 2012

Study information

• Verified date: March 2013
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCzech Republic: State Institute for Drug ControlPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRomania: National Medicines AgencySpain: Agencia Española de Medicamentos y Productos SanitariosUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

To evaluate the effects of paricalcitol capsules on cardiac structure and function over 48 weeks in patients with Stage 3/4 chronic kidney disease (CKD) who had left ventricular hypertrophy (LVH).

Description:

Patients who met the inclusion criteria and did not meet any of the exclusion criteria were randomized in a 1:1 ratio to each treatment group to receive paricalcitol capsules or placebo. A stratified randomization scheme was used to ensure balance among treatment groups with respect to country, gender, and baseline renin angiotensin-aldosterone system (RAAS) inhibitor use (yes/no).

Participants who completed the 48-Week Treatment Period could continue on in the ongoing Long-term Follow-up Period that was to last 18 months, with study visits at 6 months, 12 months and 18 months post Treatment Week 48 Visit. Participants did not receive study drug, nor were they to have undergone echocardiogram/MRI procedures during the Long-term Follow-up Period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 227
• Est. completion date: March 2012
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Estimated glomerular filtration rate (GFR) between 15-60 mL/min/1.73 m^2

• Serum intact parathyroid hormone (iPTH) value between 50-300 pg/mL

• Corrected serum calcium level 8.0-10.0 mg/dL (2.0-2.5 mmol/L)

• Phosphorous level less than or equal to 5.2 mg/dL (1.68 mmol/L)

• Serum albumin greater than or equal to 3.0 g/dL (30 g/L)

• Echocardiogram results of:

• Females: Left ventricular (LV) ejection fraction greater than or equal to 50% and septal wall thickness between 11-17 mm; and,

• Males: LV ejection fraction greater than or equal to 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. However, the subject may have switched to different brands but at equivalent doses as determined by the study physician during the month prior to the Screening Period.

• Subject must have a technically adequate baseline cardiac magnetic resonance imaging (MRI).

Exclusion Criteria:

• Subject has previously been on active vitamin D therapy within the four weeks prior to the Screening Period

• Pregnant or lactating females

• Subject is expected to initiate renal replacement therapy within one year

• Subject is taking calcitonin, bisphosphonates, cinacalcet, glucocorticoids (except topical or inhaled glucocorticoids)

• Subject had clinically significant coronary artery disease (CAD) within 3 months prior to the Screening Period, defined as either hospitalization for myocardial infarction (MI) or unstable angina; new onset angina with positive functional study or coronary angiogram revealing stenosis; or coronary revascularization procedure.

• Subject had major cardiac valve abnormality linked with LVH and/or diastolic dysfunction, defined as either aortic valve area = 1.5 cm^2 or a mean gradient of > 20 mmHg; or regurgitation lesions; more than moderate mitral regurgitation, or more than moderate aortic regurgitation.

• Subject had asymmetric septal hypertrophy defined as septal wall thickness/posterior wall thickness ratio > 1.5 based on screening echocardiogram.

• Subject had a severe cerebrovascular accident (CVA) within the last 3 months (e.g., hemorrhagic) prior to screening.

• Subject had full remission from a malignancy for less than 1 year except completely excised non-melanoma skin cancer (e.g., basal or squamous carcinoma) or any history of bone metastasis.

• Subject had comorbid conditions (e.g., advanced malignancy, advanced liver disease) with a life expectancy less than 1 year.

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
• Hypertrophy
• Hypertrophy, Left Ventricular
• Kidney Diseases
• Left Ventricular Hypertrophy
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• paricalcitol
2 µg capsule
• placebo
placebo capsule

Locations

Country	Name	City	State
Australia	Site Reference ID/Investigator# 8493	Adelaide
Australia	Site Reference ID/Investigator# 8506	Liverpool
Australia	Site Reference ID/Investigator# 8507	Parkville
Australia	Site Reference ID/Investigator# 9581	Reservoir
Australia	Site Reference ID/Investigator# 9582	Richmond
Australia	Site Reference ID/Investigator# 8500	Westmead
Czech Republic	Site Reference ID/Investigator# 8245	Prague
Czech Republic	Site Reference ID/Investigator# 8246	Prague 4
Czech Republic	Site Reference ID/Investigator# 8499	Prague 6
Germany	Site Reference ID/Investigator# 6692	Dortmund
Germany	Site Reference ID/Investigator# 9723	Duesseldorf
Germany	Site Reference ID/Investigator# 6630	Luebeck
Germany	Site Reference ID/Investigator# 7268	Nettetal
Germany	Site Reference ID/Investigator# 6622	Wuerzburg
Italy	Site Reference ID/Investigator# 10626	Lido di Camaiore
Italy	Site Reference ID/Investigator# 8070	Naples
Italy	Site Reference ID/Investigator# 8060	Rome
Poland	Site Reference ID/Investigator# 8519	Lodz
Puerto Rico	Site Reference ID/Investigator# 7702	Humacao
Puerto Rico	Site Reference ID/Investigator# 7269	Ponce
Puerto Rico	Site Reference ID/Investigator# 7818	Rio Piedras
Puerto Rico	Site Reference ID/Investigator# 7270	San Juan
Puerto Rico	Site Reference ID/Investigator# 7712	San Juan
Puerto Rico	Site Reference ID/Investigator# 7266	Toa Baja
Romania	Site Reference ID/Investigator# 8518	Bucharest
Romania	Site Reference ID/Investigator# 8881	Bucharest
Romania	Site Reference ID/Investigator# 8514	Iasi
Russian Federation	Site Reference ID/Investigator# 22682	Moscow
Russian Federation	Site Reference ID/Investigator# 7250	Moscow
Russian Federation	Site Reference ID/Investigator# 7251	Moscow
Russian Federation	Site Reference ID/Investigator# 8009	Moscow
Spain	Site Reference ID/Investigator# 8358	Barcelona
Spain	Site Reference ID/Investigator# 8883	Barcelona
Spain	Site Reference ID/Investigator# 8355	Madrid
Spain	Site Reference ID/Investigator# 8356	Madrid
Spain	Site Reference ID/Investigator# 8882	Santander (Cantabria)
Taiwan	Site Reference ID/Investigator# 8234	Hsin-Chuang City
Taiwan	Site Reference ID/Investigator# 8228	Taipei
Taiwan	Site Reference ID/Investigator# 8884	Taipei
Taiwan	Site Reference ID/Investigator# 8229	Taoyuan
United Kingdom	Site Reference ID/Investigator# 8823	Coventry
United States	Site Reference ID/Investigator# 7826	Allentown	Pennsylvania
United States	Site Reference ID/Investigator# 7816	Bethesda	Maryland
United States	Site Reference ID/Investigator# 8865	Chattanooga	Tennessee
United States	Site Reference ID/Investigator# 7823	Chicago	Illinois
United States	Site Reference ID/Investigator# 7727	Denver	Colorado
United States	Site Reference ID/Investigator# 7245	Detroit	Michigan
United States	Site Reference ID/Investigator# 7249	Evergreen Park	Illinois
United States	Site Reference ID/Investigator# 7263	Fairfax	Virginia
United States	Site Reference ID/Investigator# 7261	Houston	Texas
United States	Site Reference ID/Investigator# 8058	Houston	Texas
United States	Site Reference ID/Investigator# 8868	Kansas City	Missouri
United States	Site Reference ID/Investigator# 18882	Meridian	Idaho
United States	Site Reference ID/Investigator# 8861	Miami	Florida
United States	Site Reference ID/Investigator# 7825	Murray	Utah
United States	Site Reference ID/Investigator# 14442	Omaha	Nebraska
United States	Site Reference ID/Investigator# 7260	Orlando	Florida
United States	Site Reference ID/Investigator# 8062	Phoenix	Arizona
United States	Site Reference ID/Investigator# 8866	Provo	Utah
United States	Site Reference ID/Investigator# 18881	Rockville	Maryland
United States	Site Reference ID/Investigator# 7248	Royal Oak	Michigan
United States	Site Reference ID/Investigator# 7830	San Antonio	Texas
United States	Site Reference ID/Investigator# 8864	San Diego	California
United States	Site Reference ID/Investigator# 7257	San Dimas	California
United States	Site Reference ID/Investigator# 7817	Springfield	Massachusetts
United States	Site Reference ID/Investigator# 7828	St. Louis	Missouri
United States	Site Reference ID/Investigator# 7725	Tampa	Florida
United States	Site Reference ID/Investigator# 7824	Tampa	Florida
United States	Site Reference ID/Investigator# 8867	Tempe	Arizona
United States	Site Reference ID/Investigator# 6567	Winston-Salem	North Carolina
United States	Site Reference ID/Investigator# 7262	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)	Massachusetts General Hospital

Countries where clinical trial is conducted

United States,  Australia,  Czech Republic,  Germany,  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)	The Central Cardiac MRI Core Laboratory (CCL) interpreted and analyzed all cardiac MRI data. Left Ventricular Mass (LVM) was normalized to the participant's height by the following equation to obtain LVMI: LVM (grams) divided by height (meters)^2.7.	Baseline to 48 weeks	No
Secondary	Change in Diastolic Mitral Annular Relaxation Velocity (E')	Diastolic mitral annular relaxation velocity (lateral E wave velocity; E') is a measure of diastolic function.	Baseline to 48 weeks	No
Secondary	Change in Ratio of Peak E Wave Velocity to Lateral E Wave Velocity (E/E')	The ratio of peak E wave velocity to lateral E wave velocity (E/E') is a measure of diastolic function.	Baseline to 48 weeks	No
Secondary	Change in E-wave Deceleration Time (DT)	E-wave deceleration time (DT) is a measure of diastolic function.	Baseline to 48 weeks	No
Secondary	Change in Isovolumetric Relaxation Time (IVRT)	Isovolumetric relaxation time (IVRT) is a measure of diastolic function.	Baseline to 48 weeks	No
Secondary	Change in Left Atrial Volume	Left atrial volume is a measure of diastolic function.	Baseline to 48 weeks	No
Secondary	Change in Plasma Triiodothyronine (T3)	Plasma triiodothyronine (T3) is a biological and inflammatory marker.	Baseline to 48 weeks	No
Secondary	Change in Interleukin-6 (IL-6)	Interleukin-6 (IL-6) is a biological and inflammatory marker.	Baseline to 48 weeks	No
Secondary	Change in Troponin-T	Troponin-T is a biological and inflammatory marker.	Baseline to 48 weeks	No
Secondary	Change in B-type Natriuretic Peptide (BNP)	B-type natriuretic peptide (BNP) is a biological and inflammatory marker.	Baseline to 48 weeks	No
Secondary	Change in High Sensitivity C-reactive Protein (hsCRP)	High sensitivity C-reactive protein (hsCRP) is a biological and inflammatory marker.	Baseline to 48 weeks	No
Secondary	Change in Progression of Thoraco-abdominal Aortic Plaque Volume	Change from baseline to Week 48 in thoraco-abdominal aortic plaque volume.	Baseline to 48 weeks	No
Secondary	Change in Progression of Thoraco-abdominal Aortic Wall Volume	Change from baseline to Week 48 in thoraco-abdominal aortic wall volume	Baseline to 48 weeks	No
Secondary	Change in Progression of Aortic Compliance	Change from baseline to Week 48 in aortic compliance.	Baseline to 48 weeks	No
Secondary	Change in Progression of Left Ventricular End-systolic Volume Index	Change from baseline to Week 48 in left ventricular end-systolic volume index.	Baseline to 48 weeks	No
Secondary	Change in Progression of Left Ventricular End-diastolic Volume Index	Change from baseline to Week 48 in left ventricular end-diastolic volume index.	Baseline to 48 weeks	No
Secondary	Change in Progression of Left Ventricular Ejection Fraction	Change from baseline to Week 48 in left ventricular ejection fraction.	Baseline to 48 weeks	No

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