The PRIMO Study: Paricalcitol Capsules Benefits in Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease Stage 3/4
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 227
- 试验地点
- 71
- 主要终点
- Change From Baseline in Left Ventricular Mass Index (LVMI) Over 48 Weeks Measured by Cardiac Magnetic Resonance Imaging (MRI)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: paricalcitol (Drug)
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.
干预措施: placebo (Drug)
结局指标
主要结局
Change From Baseline in Left Ventricular Mass Index (LVMI) Over 48 Weeks Measured by Cardiac Magnetic Resonance Imaging (MRI)
时间窗: 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.
次要结局
- Change in Left Atrial Volume(Baseline to 48 weeks)
- Change in Progression of Aortic Compliance(Baseline to 48 weeks)
- Change in Plasma Triiodothyronine (T3)(Baseline to 48 weeks)
- Change in High Sensitivity C-reactive Protein (hsCRP)(Baseline to 48 weeks)
- Change in Progression of Thoraco-abdominal Aortic Plaque Volume(Baseline to 48 weeks)
- Change in Progression of Left Ventricular End-systolic Volume Index(Baseline to 48 weeks)
- Change in Ratio of Peak E Wave Velocity to Lateral E Wave Velocity (E/E')(Baseline to 48 weeks)
- Change in Isovolumetric Relaxation Time (IVRT)(Baseline to 48 weeks)
- Change in Progression of Left Ventricular Ejection Fraction(Baseline to 48 weeks)
- Change in Diastolic Mitral Annular Relaxation Velocity (E')(Baseline to 48 weeks)
- Change in Progression of Thoraco-abdominal Aortic Wall Volume(Baseline to 48 weeks)
- Change in E-wave Deceleration Time (DT)(Baseline to 48 weeks)
- Change in Interleukin-6 (IL-6)(Baseline to 48 weeks)
- Change in Troponin-T(Baseline to 48 weeks)
- Change in B-type Natriuretic Peptide (BNP)(Baseline to 48 weeks)
- Change in Progression of Left Ventricular End-diastolic Volume Index(Baseline to 48 weeks)