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

NCT00497146 | Completed Phase 3 Results DMC

• 2 other identifiers: M10-0302007-001689-34
• Study Type: interventional
• Target: 227
• Locations: 12 countries
• Sites: 71

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).

Conditions

Chronic Kidney Disease; Left Ventricular Hypertrophy

Keywords

paricalcitol; Zemplar; PRIMO; Chronic Kidney Disease Stage 3B/4

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (16)

• Change in Diastolic Mitral Annular Relaxation Velocity (E')

  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 E-wave Deceleration Time (DT)

  Baseline to 48 weeks

• Change in Isovolumetric Relaxation Time (IVRT)

  Baseline to 48 weeks

• Change in Left Atrial Volume

  Baseline to 48 weeks

Study Arms (2)

Paricalcitol

EXPERIMENTAL

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.

Drug: paricalcitol

Placebo

PLACEBO COMPARATOR

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.

Drug: placebo

Interventions

paricalcitol DRUG

2 µg capsule

Also known as: ABT-358, Zemplar

Paricalcitol

placebo DRUG

placebo capsule

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead
• Massachusetts General Hospital: collaborator

Study Sites (71)

Site Reference ID/Investigator# 8062

Phoenix, Arizona, 85012, United States

Location

Site Reference ID/Investigator# 8867

Tempe, Arizona, 85284, United States

Location

Site Reference ID/Investigator# 8864

San Diego, California, 92123, United States

Location

Site Reference ID/Investigator# 7257

San Dimas, California, 91773, United States

Location

Site Reference ID/Investigator# 7727

Denver, Colorado, 80230, United States

Location

Site Reference ID/Investigator# 8861

Miami, Florida, 33136, United States

Location

Site Reference ID/Investigator# 7260

Orlando, Florida, 32806, United States

Location

Site Reference ID/Investigator# 7725

Tampa, Florida, 33603, United States

Location

Site Reference ID/Investigator# 7824

Tampa, Florida, 33614, United States

Location

Site Reference ID/Investigator# 18882

Meridian, Idaho, 83642, United States

Location

Site Reference ID/Investigator# 7823

Chicago, Illinois, 60617, United States

Location

Site Reference ID/Investigator# 7249

Evergreen Park, Illinois, 60805, United States

Location

Site Reference ID/Investigator# 7816

Bethesda, Maryland, 20814, United States

Location

Site Reference ID/Investigator# 18881

Rockville, Maryland, 20852, United States

Location

Site Reference ID/Investigator# 7817

Springfield, Massachusetts, 01107, United States

Location

Site Reference ID/Investigator# 7245

Detroit, Michigan, 48202, United States

Location

Site Reference ID/Investigator# 7248

Royal Oak, Michigan, 48073, United States

Location

Site Reference ID/Investigator# 8868

Kansas City, Missouri, 64128, United States

Location

Site Reference ID/Investigator# 7828

St Louis, Missouri, 63110, United States

Location

Site Reference ID/Investigator# 14442

Omaha, Nebraska, 68131-3403, United States

Location

Site Reference ID/Investigator# 6567

Winston-Salem, North Carolina, 27103, United States

Location

Site Reference ID/Investigator# 7262

Winston-Salem, North Carolina, 27157-1045, United States

Location

Site Reference ID/Investigator# 7826

Allentown, Pennsylvania, 18103, United States

Location

Site Reference ID/Investigator# 8865

Chattanooga, Tennessee, 37404, United States

Location

Site Reference ID/Investigator# 7261

Houston, Texas, 77004, United States

Location

Site Reference ID/Investigator# 8058

Houston, Texas, 77099, United States

Location

Site Reference ID/Investigator# 7830

San Antonio, Texas, 78229, United States

Location

Site Reference ID/Investigator# 7825

Murray, Utah, 84157-7000, United States

Location

Site Reference ID/Investigator# 8866

Provo, Utah, 84604, United States

Location

Site Reference ID/Investigator# 7263

Fairfax, Virginia, 22033, United States

Location

Site Reference ID/Investigator# 8493

Adelaide, 5000, Australia

Location

Site Reference ID/Investigator# 8506

Liverpool, 2170, Australia

Location

Site Reference ID/Investigator# 8507

Parkville, 3050, Australia

Location

Site Reference ID/Investigator# 9581

Reservoir, 3073, Australia

Location

Site Reference ID/Investigator# 9582

Richmond, 3121, Australia

Location

Site Reference ID/Investigator# 8500

Westmead, 2145, Australia

Location

Site Reference ID/Investigator# 8245

Prague, 12808, Czechia

Location

Site Reference ID/Investigator# 8246

Prague, 14021, Czechia

Location

Site Reference ID/Investigator# 8499

Prague, 16900, Czechia

Location

Site Reference ID/Investigator# 6692

Dortmund, 44263, Germany

Location

Site Reference ID/Investigator# 9723

Düsseldorf, 40210, Germany

Location

Site Reference ID/Investigator# 6630

Lübeck, 23538, Germany

Location

Site Reference ID/Investigator# 7268

Nettetal, 41334, Germany

Location

Site Reference ID/Investigator# 6622

Würzburg, 97080, Germany

Location

Site Reference ID/Investigator# 10626

Lido di Camaiore, 55041, Italy

Location

Site Reference ID/Investigator# 8070

Naples, 80131, Italy

Location

Site Reference ID/Investigator# 8060

Rome, 00165, Italy

Location

Site Reference ID/Investigator# 8519

Lodz, 90-153, Poland

Location

Site Reference ID/Investigator# 7702

Humacao, 00791, Puerto Rico

Location

Site Reference ID/Investigator# 7269

Ponce, 00717-1322, Puerto Rico

Location

Site Reference ID/Investigator# 7818

Rio Piedras, 00935, Puerto Rico

Location

Site Reference ID/Investigator# 7270

San Juan, 00909, Puerto Rico

Location

Site Reference ID/Investigator# 7712

San Juan, 00918, Puerto Rico

Location

Site Reference ID/Investigator# 7266

Toa Baja, 00949, Puerto Rico

Location

Site Reference ID/Investigator# 8881

Bucharest, 010731, Romania

Location

Site Reference ID/Investigator# 8518

Bucharest, 022328, Romania

Location

Site Reference ID/Investigator# 8514

Iași, 700503, Romania

Location

Site Reference ID/Investigator# 22682

Moscow, 105229, Russia

Location

Site Reference ID/Investigator# 8009

Moscow, 123182, Russia

Location

Site Reference ID/Investigator# 7251

Moscow, 125284, Russia

Location

Site Reference ID/Investigator# 7250

Moscow, 127473, Russia

Location

Site Reference ID/Investigator# 8883

Barcelona, 08003, Spain

Location

Site Reference ID/Investigator# 8358

Barcelona, 08035, Spain

Location

Site Reference ID/Investigator# 8355

Madrid, 28007, Spain

Location

Site Reference ID/Investigator# 8356

Madrid, 28041, Spain

Location

Site Reference ID/Investigator# 8882

Santander (Cantabria), 39008, Spain

Location

Site Reference ID/Investigator# 8884

Taipei, 10002, Taiwan

Location

Site Reference ID/Investigator# 8228

Taipei, Taiwan

Location

Site Reference ID/Investigator# 8229

Taoyuan District, Taiwan

Location

Site Reference ID/Investigator# 8234

Xinzhuang, Taiwan

Location

Site Reference ID/Investigator# 8823

Coventry, CV2 2DX, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 23194491 DERIVED

• 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.

  PMID: 22337679 DERIVED

• 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.

  PMID: 21242674 DERIVED

• 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.

  PMID: 18591942 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hypertrophy, Left Ventricular

Interventions

paricalcitol

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Hypertrophy; Pathological Conditions, Anatomical

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie (prior sponsor, Abbott)

800-633-9110

Study Officials

• Ann Eldred, MD

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2007
• First Posted: July 6, 2007
• Study Start: February 1, 2008
• Primary Completion: September 1, 2010
• Study Completion: March 1, 2012
• Last Updated: March 12, 2013
• Results First Posted: December 23, 2011

Record last verified: 2013-03

Locations

DE (5); CZ (3); PR (6); US (30); IT (3); RO (3); RU (4); AU (6); ES (5); GB (1); PL (1); TW (4)