The PRIMO Study: Paricalcitol Capsules Benefits Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease Stage 3/4
- Conditions
- Chronic Kidney DiseaseLeft Ventricular Hypertrophy
- Interventions
- Drug: placebo
- Registration Number
- NCT00497146
- Lead Sponsor
- AbbVie (prior sponsor, Abbott)
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 227
-
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).
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo placebo Participants received 2 placebo capsules once a day for up to 48 weeks. Participants who completed the 48-week Treatment Period could continue in the Long-term Follow-up Period for an additional 18 months. Participants did not receive study drug during the Long-term Follow-up Period. Paricalcitol paricalcitol Participants received paricalcitol capsules 2 µg once a day (two 1 µg paricalcitol capsules), for up to 48 weeks. Participants who completed the 48-week Treatment Period could continue in the Long-term Follow-up Period for an additional 18 months. Participants did not receive study drug during the Long-term Follow-up Period.
- Primary Outcome Measures
Name Time Method Change From Baseline in Left Ventricular Mass Index (LVMI) Over 48 Weeks Measured by Cardiac Magnetic Resonance Imaging (MRI) Baseline to 48 weeks 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.
- Secondary Outcome Measures
Name Time Method Change in Ratio of Peak E Wave Velocity to Lateral E Wave Velocity (E/E') Baseline to 48 weeks The ratio of peak E wave velocity to lateral E wave velocity (E/E') is a measure of diastolic function.
Change in Isovolumetric Relaxation Time (IVRT) Baseline to 48 weeks Isovolumetric relaxation time (IVRT) is a measure of diastolic function.
Change in Left Atrial Volume Baseline to 48 weeks Left atrial volume is a measure of diastolic function.
Change in Progression of Aortic Compliance Baseline to 48 weeks Change from baseline to Week 48 in aortic compliance.
Change in Plasma Triiodothyronine (T3) Baseline to 48 weeks Plasma triiodothyronine (T3) is a biological and inflammatory marker.
Change in High Sensitivity C-reactive Protein (hsCRP) Baseline to 48 weeks High sensitivity C-reactive protein (hsCRP) is a biological and inflammatory marker.
Change in Progression of Thoraco-abdominal Aortic Plaque Volume Baseline to 48 weeks Change from baseline to Week 48 in thoraco-abdominal aortic plaque volume.
Change in Progression of Left Ventricular End-systolic Volume Index Baseline to 48 weeks Change from baseline to Week 48 in left ventricular end-systolic volume index.
Change in Progression of Left Ventricular Ejection Fraction Baseline to 48 weeks Change from baseline to Week 48 in left ventricular ejection fraction.
Change in Diastolic Mitral Annular Relaxation Velocity (E') Baseline to 48 weeks Diastolic mitral annular relaxation velocity (lateral E wave velocity; E') is a measure of diastolic function.
Change in Progression of Thoraco-abdominal Aortic Wall Volume Baseline to 48 weeks Change from baseline to Week 48 in thoraco-abdominal aortic wall volume
Change in E-wave Deceleration Time (DT) Baseline to 48 weeks E-wave deceleration time (DT) is a measure of diastolic function.
Change in Interleukin-6 (IL-6) Baseline to 48 weeks Interleukin-6 (IL-6) is a biological and inflammatory marker.
Change in Troponin-T Baseline to 48 weeks Troponin-T is a biological and inflammatory marker.
Change in B-type Natriuretic Peptide (BNP) Baseline to 48 weeks B-type natriuretic peptide (BNP) is a biological and inflammatory marker.
Change in Progression of Left Ventricular End-diastolic Volume Index Baseline to 48 weeks Change from baseline to Week 48 in left ventricular end-diastolic volume index.
Trial Locations
- Locations (71)
Site Reference ID/Investigator# 7251
🇷🇺Moscow, Russian Federation
Site Reference ID/Investigator# 8228
🇨🇳Taipei, Taiwan
Site Reference ID/Investigator# 8881
🇷🇴Bucharest, Romania
Site Reference ID/Investigator# 8518
🇷🇴Bucharest, Romania
Site Reference ID/Investigator# 8867
🇺🇸Tempe, Arizona, United States
Site Reference ID/Investigator# 7257
🇺🇸San Dimas, California, United States
Site Reference ID/Investigator# 7261
🇺🇸Houston, Texas, United States
Site Reference ID/Investigator# 8058
🇺🇸Houston, Texas, United States
Site Reference ID/Investigator# 7263
🇺🇸Fairfax, Virginia, United States
Site Reference ID/Investigator# 8062
🇺🇸Phoenix, Arizona, United States
Site Reference ID/Investigator# 8864
🇺🇸San Diego, California, United States
Site Reference ID/Investigator# 7245
🇺🇸Detroit, Michigan, United States
Site Reference ID/Investigator# 7830
🇺🇸San Antonio, Texas, United States
Site Reference ID/Investigator# 8070
🇮🇹Naples, Italy
Site Reference ID/Investigator# 7816
🇺🇸Bethesda, Maryland, United States
Site Reference ID/Investigator# 7727
🇺🇸Denver, Colorado, United States
Site Reference ID/Investigator# 7725
🇺🇸Tampa, Florida, United States
Site Reference ID/Investigator# 7824
🇺🇸Tampa, Florida, United States
Site Reference ID/Investigator# 8861
🇺🇸Miami, Florida, United States
Site Reference ID/Investigator# 18882
🇺🇸Meridian, Idaho, United States
Site Reference ID/Investigator# 7823
🇺🇸Chicago, Illinois, United States
Site Reference ID/Investigator# 18881
🇺🇸Rockville, Maryland, United States
Site Reference ID/Investigator# 7817
🇺🇸Springfield, Massachusetts, United States
Site Reference ID/Investigator# 7249
🇺🇸Evergreen Park, Illinois, United States
Site Reference ID/Investigator# 8868
🇺🇸Kansas City, Missouri, United States
Site Reference ID/Investigator# 7828
🇺🇸St. Louis, Missouri, United States
Site Reference ID/Investigator# 7826
🇺🇸Allentown, Pennsylvania, United States
Site Reference ID/Investigator# 14442
🇺🇸Omaha, Nebraska, United States
Site Reference ID/Investigator# 8865
🇺🇸Chattanooga, Tennessee, United States
Site Reference ID/Investigator# 7825
🇺🇸Murray, Utah, United States
Site Reference ID/Investigator# 8493
🇦🇺Adelaide, Australia
Site Reference ID/Investigator# 8866
🇺🇸Provo, Utah, United States
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, Australia
Site Reference ID/Investigator# 8245
🇨🇿Prague, Czech Republic
Site Reference ID/Investigator# 8246
🇨🇿Prague 4, Czech Republic
Site Reference ID/Investigator# 8499
🇨🇿Prague 6, Czech Republic
Site Reference ID/Investigator# 6630
🇩🇪Luebeck, Germany
Site Reference ID/Investigator# 6692
🇩🇪Dortmund, Germany
Site Reference ID/Investigator# 9723
🇩🇪Duesseldorf, Germany
Site Reference ID/Investigator# 6622
🇩🇪Wuerzburg, Germany
Site Reference ID/Investigator# 7268
🇩🇪Nettetal, Germany
Site Reference ID/Investigator# 10626
🇮🇹Lido di Camaiore, Italy
Site Reference ID/Investigator# 8519
🇵🇱Lodz, Poland
Site Reference ID/Investigator# 8060
🇮🇹Rome, Italy
Site Reference ID/Investigator# 7269
🇵🇷Ponce, Puerto Rico
Site Reference ID/Investigator# 7702
🇵🇷Humacao, Puerto Rico
Site Reference ID/Investigator# 7266
🇵🇷Toa Baja, Puerto Rico
Site Reference ID/Investigator# 7818
🇵🇷Rio Piedras, Puerto Rico
Site Reference ID/Investigator# 7712
🇵🇷San Juan, Puerto Rico
Site Reference ID/Investigator# 7270
🇵🇷San Juan, Puerto Rico
Site Reference ID/Investigator# 8514
🇷🇴Iasi, Romania
Site Reference ID/Investigator# 22682
🇷🇺Moscow, Russian Federation
Site Reference ID/Investigator# 8009
🇷🇺Moscow, Russian Federation
Site Reference ID/Investigator# 8883
🇪🇸Barcelona, Spain
Site Reference ID/Investigator# 8358
🇪🇸Barcelona, Spain
Site Reference ID/Investigator# 8884
🇨🇳Taipei, Taiwan
Site Reference ID/Investigator# 8234
🇨🇳Hsin-Chuang City, Taiwan
Site Reference ID/Investigator# 8882
🇪🇸Santander (Cantabria), Spain
Site Reference ID/Investigator# 8356
🇪🇸Madrid, Spain
Site Reference ID/Investigator# 7250
🇷🇺Moscow, Russian Federation
Site Reference ID/Investigator# 8229
🇨🇳Taoyuan, Taiwan
Site Reference ID/Investigator# 8823
🇬🇧Coventry, United Kingdom
Site Reference ID/Investigator# 8355
🇪🇸Madrid, Spain
Site Reference ID/Investigator# 6567
🇺🇸Winston-Salem, North Carolina, United States
Site Reference ID/Investigator# 7260
🇺🇸Orlando, Florida, United States
Site Reference ID/Investigator# 7262
🇺🇸Winston-Salem, North Carolina, United States
Site Reference ID/Investigator# 7248
🇺🇸Royal Oak, Michigan, United States