Clinical trial NCT00497146: The PRIMO Study: Paricalcitol Capsules Benefits Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease Stage 3/4
Official title: The PRIMO Study: Paricalcitol Capsules Benefits in Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease Stage 3/4
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Kidney Disease
Left Ventricular Hypertrophy
Keywords: paricalcitol
Zemplar
PRIMO
Chronic Kidney Disease Stage 3B/4
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Massachusetts General Hospital
First posted: 2007-07-06
Enrollment: 227
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 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Left Ventricular Mass Index (LVMI) Over 48 Weeks Measured by Cardiac Magnetic Resonance Imaging (MRI)
timeFrame: Baseline to 48 weeks
Secondary outcomes:
measure: Change in Diastolic Mitral Annular Relaxation Velocity (E')
timeFrame: Baseline to 48 weeks
measure: Change in Ratio of Peak E Wave Velocity to Lateral E Wave Velocity (E/E')
timeFrame: Baseline to 48 weeks
measure: Change in E-wave Deceleration Time (DT)
timeFrame: Baseline to 48 weeks
measure: Change in Isovolumetric Relaxation Time (IVRT)
timeFrame: Baseline to 48 weeks
measure: Change in Left Atrial Volume
timeFrame: Baseline to 48 weeks
measure: Change in Plasma Triiodothyronine (T3)
timeFrame: Baseline to 48 weeks
measure: Change in Interleukin-6 (IL-6)
timeFrame: Baseline to 48 weeks
measure: Change in Troponin-T
timeFrame: Baseline to 48 weeks
measure: Change in B-type Natriuretic Peptide (BNP)
timeFrame: Baseline to 48 weeks
measure: Change in High Sensitivity C-reactive Protein (hsCRP)
timeFrame: Baseline to 48 weeks
measure: Change in Progression of Thoraco-abdominal Aortic Plaque Volume
timeFrame: Baseline to 48 weeks
measure: Change in Progression of Thoraco-abdominal Aortic Wall Volume
timeFrame: Baseline to 48 weeks
measure: Change in Progression of Aortic Compliance
timeFrame: Baseline to 48 weeks
measure: Change in Progression of Left Ventricular End-systolic Volume Index
timeFrame: Baseline to 48 weeks
measure: Change in Progression of Left Ventricular End-diastolic Volume Index
timeFrame: Baseline to 48 weeks
measure: Change in Progression of Left Ventricular Ejection Fraction
timeFrame: Baseline to 48 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Site Reference ID/Investigator# 8062
state: Arizona
city: Tempe
country: United States
facility: Site Reference ID/Investigator# 8867
state: Arizona
city: San Diego
country: United States
facility: Site Reference ID/Investigator# 8864
state: California
city: San Dimas
country: United States
facility: Site Reference ID/Investigator# 7257
state: California
city: Denver
country: United States
facility: Site Reference ID/Investigator# 7727
state: Colorado
city: Miami
country: United States
facility: Site Reference ID/Investigator# 8861
state: Florida
city: Orlando
country: United States
facility: Site Reference ID/Investigator# 7260
state: Florida
city: Tampa
country: United States
facility: Site Reference ID/Investigator# 7725
state: Florida
city: Tampa
country: United States
facility: Site Reference ID/Investigator# 7824
state: Florida
city: Meridian
country: United States
facility: Site Reference ID/Investigator# 18882
state: Idaho
city: Chicago
country: United States
facility: Site Reference ID/Investigator# 7823
state: Illinois
city: Evergreen Park
country: United States
facility: Site Reference ID/Investigator# 7249
state: Illinois
city: Bethesda
country: United States
facility: Site Reference ID/Investigator# 7816
state: Maryland
city: Rockville
country: United States
facility: Site Reference ID/Investigator# 18881
state: Maryland
city: Springfield
country: United States
facility: Site Reference ID/Investigator# 7817
state: Massachusetts
city: Detroit
country: United States
facility: Site Reference ID/Investigator# 7245
state: Michigan
city: Royal Oak
country: United States
facility: Site Reference ID/Investigator# 7248
state: Michigan
city: Kansas City
country: United States
facility: Site Reference ID/Investigator# 8868
state: Missouri
city: St. Louis
country: United States
facility: Site Reference ID/Investigator# 7828
state: Missouri
city: Omaha
country: United States
facility: Site Reference ID/Investigator# 14442
state: Nebraska
city: Winston-Salem
country: United States
facility: Site Reference ID/Investigator# 6567
state: North Carolina
city: Winston-Salem
country: United States
facility: Site Reference ID/Investigator# 7262
state: North Carolina
city: Allentown
country: United States
facility: Site Reference ID/Investigator# 7826
state: Pennsylvania
city: Chattanooga
country: United States
facility: Site Reference ID/Investigator# 8865
state: Tennessee
city: Houston
country: United States
facility: Site Reference ID/Investigator# 7261
state: Texas
city: Houston
country: United States
facility: Site Reference ID/Investigator# 8058
state: Texas
city: San Antonio
country: United States
facility: Site Reference ID/Investigator# 7830
state: Texas
city: Murray
country: United States
facility: Site Reference ID/Investigator# 7825
state: Utah
city: Provo
country: United States
facility: Site Reference ID/Investigator# 8866
state: Utah
city: Fairfax
country: United States
facility: Site Reference ID/Investigator# 7263
state: Virginia
city: Adelaide
country: Australia
facility: Site Reference ID/Investigator# 8493
city: Liverpool
country: Australia
facility: Site Reference ID/Investigator# 8506
city: Parkville
country: Australia
facility: Site Reference ID/Investigator# 8507
city: Reservoir
country: Australia
facility: Site Reference ID/Investigator# 9581
city: Richmond
country: Australia
facility: Site Reference ID/Investigator# 9582
city: Westmead
country: Australia
facility: Site Reference ID/Investigator# 8500
city: Prague 4
country: Czech Republic
facility: Site Reference ID/Investigator# 8246
city: Prague 6
country: Czech Republic
facility: Site Reference ID/Investigator# 8499
city: Prague
country: Czech Republic
facility: Site Reference ID/Investigator# 8245
city: Dortmund
country: Germany
facility: Site Reference ID/Investigator# 6692
city: Duesseldorf
country: Germany
facility: Site Reference ID/Investigator# 9723
city: Luebeck
country: Germany
facility: Site Reference ID/Investigator# 6630
city: Nettetal
country: Germany
facility: Site Reference ID/Investigator# 7268
city: Wuerzburg
country: Germany
facility: Site Reference ID/Investigator# 6622
city: Lido di Camaiore
country: Italy
facility: Site Reference ID/Investigator# 10626
city: Naples
country: Italy
facility: Site Reference ID/Investigator# 8070
city: Rome
country: Italy
facility: Site Reference ID/Investigator# 8060
city: Lodz
country: Poland
facility: Site Reference ID/Investigator# 8519
city: Humacao
country: Puerto Rico
facility: Site Reference ID/Investigator# 7702
city: Ponce
country: Puerto Rico
facility: Site Reference ID/Investigator# 7269
city: Rio Piedras
country: Puerto Rico
facility: Site Reference ID/Investigator# 7818
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 7270
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 7712
city: Toa Baja
country: Puerto Rico
facility: Site Reference ID/Investigator# 7266
city: Bucharest
country: Romania
facility: Site Reference ID/Investigator# 8881
city: Bucharest
country: Romania
facility: Site Reference ID/Investigator# 8518
city: Iasi
country: Romania
facility: Site Reference ID/Investigator# 8514
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator# 22682
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator# 8009
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator# 7251
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator# 7250
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 8883
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 8358
city: Madrid
country: Spain
facility: Site Reference ID/Investigator# 8355
city: Madrid
country: Spain
facility: Site Reference ID/Investigator# 8356
city: Santander (Cantabria)
country: Spain
facility: Site Reference ID/Investigator# 8882
city: Hsin-Chuang City
country: Taiwan
facility: Site Reference ID/Investigator# 8234
city: Taipei
country: Taiwan
facility: Site Reference ID/Investigator# 8884
city: Taipei
country: Taiwan
facility: Site Reference ID/Investigator# 8228
city: Taoyuan
country: Taiwan
facility: Site Reference ID/Investigator# 8229
city: Coventry
country: United Kingdom
facility: Site Reference ID/Investigator# 8823
Study officials:
affiliation: AbbVie
name: Ann Eldred, MD
role: STUDY_DIRECTOR
References:
citation: Tamez H, Zoccali C, Packham D, Wenger J, Bhan I, Appelbaum E, Pritchett Y, Chang Y, Agarwal R, Wanner C, Lloyd-Jones D, Cannata J, Thompson BT, Andress D, Zhang W, Singh B, Zehnder D, Pachika A, Manning WJ, Shah A, Solomon SD, Thadhani R. Vitamin D reduces left atrial volume in patients with left ventricular hypertrophy and chronic kidney disease. Am Heart J. 2012 Dec;164(6):902-9.e2. doi: 10.1016/j.ahj.2012.09.018. Epub 2012 Oct 29.
citation: Thadhani R, Appelbaum E, Pritchett Y, Chang Y, Wenger J, Tamez H, Bhan I, Agarwal R, Zoccali C, Wanner C, Lloyd-Jones D, Cannata J, Thompson BT, Andress D, Zhang W, Packham D, Singh B, Zehnder D, Shah A, Pachika A, Manning WJ, Solomon SD. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. JAMA. 2012 Feb 15;307(7):674-84. doi: 10.1001/jama.2012.120.
citation: Thadhani R, Appelbaum E, Chang Y, Pritchett Y, Bhan I, Agarwal R, Zoccali C, Wanner C, Lloyd-Jones D, Cannata J, Thompson T, Audhya P, Andress D, Zhang W, Ye J, Packham D, Singh B, Zehnder D, Manning WJ, Pachika A, Solomon SD. Vitamin D receptor activation and left ventricular hypertrophy in advanced kidney disease. Am J Nephrol. 2011;33(2):139-49. doi: 10.1159/000323551. Epub 2011 Jan 18.
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.