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

NCT ID: NCT00497146

Last Updated: 2013-03-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

227 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-02-29

Study Completion Date

2012-03-31

Brief Summary

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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

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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.

Conditions

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Chronic Kidney Disease Left Ventricular Hypertrophy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

paricalcitol

Intervention Type DRUG

2 µg capsule

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.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

placebo capsule

Interventions

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paricalcitol

2 µg capsule

Intervention Type DRUG

placebo

placebo capsule

Intervention Type DRUG

Other Intervention Names

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ABT-358 Zemplar

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Massachusetts General Hospital

OTHER

Sponsor Role collaborator

AbbVie (prior sponsor, Abbott)

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ann Eldred, MD

Role: STUDY_DIRECTOR

AbbVie

Locations

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Site Reference ID/Investigator# 8062

Phoenix, Arizona, United States

Site Status

Site Reference ID/Investigator# 8867

Tempe, Arizona, United States

Site Status

Site Reference ID/Investigator# 8864

San Diego, California, United States

Site Status

Site Reference ID/Investigator# 7257

San Dimas, California, United States

Site Status

Site Reference ID/Investigator# 7727

Denver, Colorado, United States

Site Status

Site Reference ID/Investigator# 8861

Miami, Florida, United States

Site Status

Site Reference ID/Investigator# 7260

Orlando, Florida, United States

Site Status

Site Reference ID/Investigator# 7725

Tampa, Florida, United States

Site Status

Site Reference ID/Investigator# 7824

Tampa, Florida, United States

Site Status

Site Reference ID/Investigator# 18882

Meridian, Idaho, United States

Site Status

Site Reference ID/Investigator# 7823

Chicago, Illinois, United States

Site Status

Site Reference ID/Investigator# 7249

Evergreen Park, Illinois, United States

Site Status

Site Reference ID/Investigator# 7816

Bethesda, Maryland, United States

Site Status

Site Reference ID/Investigator# 18881

Rockville, Maryland, United States

Site Status

Site Reference ID/Investigator# 7817

Springfield, Massachusetts, United States

Site Status

Site Reference ID/Investigator# 7245

Detroit, Michigan, United States

Site Status

Site Reference ID/Investigator# 7248

Royal Oak, Michigan, United States

Site Status

Site Reference ID/Investigator# 8868

Kansas City, Missouri, United States

Site Status

Site Reference ID/Investigator# 7828

St Louis, Missouri, United States

Site Status

Site Reference ID/Investigator# 14442

Omaha, Nebraska, United States

Site Status

Site Reference ID/Investigator# 6567

Winston-Salem, North Carolina, United States

Site Status

Site Reference ID/Investigator# 7262

Winston-Salem, North Carolina, United States

Site Status

Site Reference ID/Investigator# 7826

Allentown, Pennsylvania, United States

Site Status

Site Reference ID/Investigator# 8865

Chattanooga, Tennessee, United States

Site Status

Site Reference ID/Investigator# 7261

Houston, Texas, United States

Site Status

Site Reference ID/Investigator# 8058

Houston, Texas, United States

Site Status

Site Reference ID/Investigator# 7830

San Antonio, Texas, United States

Site Status

Site Reference ID/Investigator# 7825

Murray, Utah, United States

Site Status

Site Reference ID/Investigator# 8866

Provo, Utah, United States

Site Status

Site Reference ID/Investigator# 7263

Fairfax, Virginia, United States

Site Status

Site Reference ID/Investigator# 8493

Adelaide, , Australia

Site Status

Site Reference ID/Investigator# 8506

Liverpool, , Australia

Site Status

Site Reference ID/Investigator# 8507

Parkville, , Australia

Site Status

Site Reference ID/Investigator# 9581

Reservoir, , Australia

Site Status

Site Reference ID/Investigator# 9582

Richmond, , Australia

Site Status

Site Reference ID/Investigator# 8500

Westmead, , Australia

Site Status

Site Reference ID/Investigator# 8245

Prague, , Czechia

Site Status

Site Reference ID/Investigator# 8246

Prague, , Czechia

Site Status

Site Reference ID/Investigator# 8499

Prague, , Czechia

Site Status

Site Reference ID/Investigator# 6692

Dortmund, , Germany

Site Status

Site Reference ID/Investigator# 9723

Düsseldorf, , Germany

Site Status

Site Reference ID/Investigator# 6630

Lübeck, , Germany

Site Status

Site Reference ID/Investigator# 7268

Nettetal, , Germany

Site Status

Site Reference ID/Investigator# 6622

Würzburg, , Germany

Site Status

Site Reference ID/Investigator# 10626

Lido di Camaiore, , Italy

Site Status

Site Reference ID/Investigator# 8070

Naples, , Italy

Site Status

Site Reference ID/Investigator# 8060

Rome, , Italy

Site Status

Site Reference ID/Investigator# 8519

Lodz, , Poland

Site Status

Site Reference ID/Investigator# 7702

Humacao, , Puerto Rico

Site Status

Site Reference ID/Investigator# 7269

Ponce, , Puerto Rico

Site Status

Site Reference ID/Investigator# 7818

Rio Piedras, , Puerto Rico

Site Status

Site Reference ID/Investigator# 7270

San Juan, , Puerto Rico

Site Status

Site Reference ID/Investigator# 7712

San Juan, , Puerto Rico

Site Status

Site Reference ID/Investigator# 7266

Toa Baja, , Puerto Rico

Site Status

Site Reference ID/Investigator# 8881

Bucharest, , Romania

Site Status

Site Reference ID/Investigator# 8518

Bucharest, , Romania

Site Status

Site Reference ID/Investigator# 8514

Iași, , Romania

Site Status

Site Reference ID/Investigator# 22682

Moscow, , Russia

Site Status

Site Reference ID/Investigator# 8009

Moscow, , Russia

Site Status

Site Reference ID/Investigator# 7251

Moscow, , Russia

Site Status

Site Reference ID/Investigator# 7250

Moscow, , Russia

Site Status

Site Reference ID/Investigator# 8883

Barcelona, , Spain

Site Status

Site Reference ID/Investigator# 8358

Barcelona, , Spain

Site Status

Site Reference ID/Investigator# 8355

Madrid, , Spain

Site Status

Site Reference ID/Investigator# 8356

Madrid, , Spain

Site Status

Site Reference ID/Investigator# 8882

Santander (Cantabria), , Spain

Site Status

Site Reference ID/Investigator# 8884

Taipei, , Taiwan

Site Status

Site Reference ID/Investigator# 8228

Taipei, , Taiwan

Site Status

Site Reference ID/Investigator# 8229

Taoyuan District, , Taiwan

Site Status

Site Reference ID/Investigator# 8234

Xinzhuang, , Taiwan

Site Status

Site Reference ID/Investigator# 8823

Coventry, , United Kingdom

Site Status

Countries

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United States Australia Czechia Germany Italy Poland Puerto Rico Romania Russia Spain Taiwan United Kingdom

References

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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.

Reference Type DERIVED
PMID: 23194491 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22337679 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21242674 (View on PubMed)

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.

Reference Type DERIVED
PMID: 18591942 (View on PubMed)

Related Links

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Other Identifiers

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2007-001689-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M10-030

Identifier Type: -

Identifier Source: org_study_id

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