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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00616902




Registration number
NCT00616902
Ethics application status
Date submitted
5/02/2008
Date registered
15/02/2008
Date last updated
20/01/2012

Titles & IDs
Public title
The PRIMO II Study: Paricalcitol Injection Benefits in Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease (CKD) Stage 5
Scientific title
Clinical Study Protocol M10-221 The PRIMO II Study: Paricalcitol Injection Benefits in Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease (CKD) Stage 5
Secondary ID [1] 0 0
2007-005092-33
Secondary ID [2] 0 0
M10-221
Universal Trial Number (UTN)
Trial acronym
PRIMO II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Kidney Disease (CKD) Stage 5 0 0
Hypertrophy, Left Ventricular 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - paricalcitol injection 4 mcg/mL
Treatment: Drugs - Placebo Injection 4 mcg/mL

Active comparator: Paricalcitol Injection 4 mcg/mL - Paricalcitol Injection 4 mcg/mL given intravenously 3 times per week during dialysis

Placebo comparator: Placebo Injection 4 mcg/mL - Placebo Injection 4 mcg/mL given intravenously three times a week during dialysis


Treatment: Drugs: paricalcitol injection 4 mcg/mL
Paricalcitol Injection 4 mcg/mL intravenously three times a week during dialysis

Treatment: Drugs: Placebo Injection 4 mcg/mL
Placebo Injection 4 mcg/mL given intravenously three times a week during dialysis
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Left Ventricular Mass Index (LVMI) Over 48 Weeks Measured by Cardiac Magnetic Resonance Imaging (MRI)
Timepoint [1] 0 0
Baseline, 24 Weeks, and 48 Weeks/Early Termination
Secondary outcome [1] 0 0
Change From Baseline in the Echocardiographic Assessment of Diastolic Function Assessed by Evaluating Changes in Diastolic Mitral Annular Relaxation Velocity (E') Over 48 Weeks.
Timepoint [1] 0 0
Baseline, 24 Weeks, and 48 Weeks/Early Termination
Secondary outcome [2] 0 0
Change From Baseline in Evaluating Changes in the Additional Measure of Diastolic Function of Isovolumetric Relaxation Time (IVRT) Over 48 Weeks.
Timepoint [2] 0 0
Baseline, 24 Weeks, and 48 Weeks/Early Termination
Secondary outcome [3] 0 0
Change From Baseline in Evaluating Changes in the Additional Measure of Diastolic Function of Peak E-wave Velocity to Lateral E-wave Velocity (E/E') Over 48 Weeks.
Timepoint [3] 0 0
Baseline, Week 24, and Week 48/Early Termination
Secondary outcome [4] 0 0
Change From Baseline in Evaluating Changes in the Additional Measure of Diastolic Function E-wave Deceleration Time (DT) Over 48 Weeks
Timepoint [4] 0 0
Baseline, 24 Weeks, and 48 Weeks/Early Termination
Secondary outcome [5] 0 0
Change From Baseline in Biological Marker Triiodothyronine (T3).
Timepoint [5] 0 0
Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)
Secondary outcome [6] 0 0
Change From Baseline in Biological Marker Plasma Troponin-T Over 48 Weeks
Timepoint [6] 0 0
Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)
Secondary outcome [7] 0 0
Change From Baseline in Biological Marker Plasma Interleukin-6 (IL-6) Over 48 Weeks
Timepoint [7] 0 0
Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)
Secondary outcome [8] 0 0
Change From Baseline in Biological Marker Plasma High Sensitivity C-reactive Protein (hsCRP) Over 48 Weeks
Timepoint [8] 0 0
Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)
Secondary outcome [9] 0 0
Change From Baseline in Biological Marker Plasma B-Type Natriuretic Peptide (BNP)
Timepoint [9] 0 0
Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)

Eligibility
Key inclusion criteria
* Stage 5 CKD receiving chronic hemodialysis three times per week for >= 3 months and <= 12 months from date of Randomization (Day 1).
* Serum intact parathyroid hormone (iPTH) value between 100-350 pg/mL.
* Serum calcium level between 8.4-10.5 mg/dL (2.1-2.6 mmol/L).
* Phosphate < 7 mg/dL.
* Serum albumin >= 3.0 g/dL (30 g/L).
* Echocardiogram results:

* For females, left ventricular (LV) ejection fraction >= 50% and septal wall thickness between 11-17 mm.
* For males, LV ejection fraction >= 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.
* A technically adequate baseline cardiac magnetic resonance imaging (MRI).
* If female, subject is not breast feeding or is not pregnant, or is not of childbearing potential, defined as postmenopausal for at least one year or surgically sterile, or is of childbearing potential and practicing one of the following methods of birth control:
* Double-barrier method
* Hormonal contraceptives for at least three months prior to and during study drug administration
* Maintains a monogamous relationship with a vasectomized partner
* Total abstinence from sexual intercourse during the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Subject has previously been on active vitamin D therapy (calcitriol, paricalcitol, doxercalciferol, alfacalcidol) for a total duration greater than three months since the start of dialysis.
* Subject has a history of an allergic reaction or significant sensitivity to paricalcitol or to drugs similar to the study drug.
* Subject is expected to receive an increased dose of RAAS inhibitor (Angiotensin converting enzyme inhibitor [ACEi], Angiotensin II receptor blocker [ARB] or aldosterone inhibitor) during the course of the study.
* Subject has clinically significant coronary artery disease (CAD) within 3 months prior to the Screening Period, defined as one of the following:

* Hospitalization for myocardial infarction (MI) or unstable angina; or
* New onset angina with positive functional study or coronary angiogram revealing stenosis; or
* Coronary revascularization procedure.
* Subject has major cardiac valve abnormality linked with left ventricular hypertrophy (LVH) and/or diastolic dysfunction, defined as one of the following:

* Aortic valve area <= 1.5 cm2 or a mean gradient of > 20 mmHg; or
* Regurgitation lesions; more than moderate mitral regurgitation or more than moderate aortic regurgitation.
* Subject has asymmetric septal hypertrophy.
* Subject has had a severe cerebrovascular accident (CVA) within the last three months (e.g., hemorrhagic) prior to screening.
* Full remission from a malignancy for less than one year except completely excised non-Melanoma skin cancer (e.g. basal or squamous carcinoma) or any history of bone metastasis.
* Subject has co-morbid conditions.
* Subject has received any investigational drug within 30 days prior to study drug administration or is currently enrolled in another clinical trial.
* Subject has poorly controlled hypertension.
* Subject has history of renal artery stenosis, primary aldosteronism or pheochromocytoma
* Subject is taking calcitonin, bisphosphonates, cinacalcet, glucocorticoids (except topical or inhaled glucocorticoids)
* Subject is currently receiving immunosuppressant therapy and/or high doses of glucocorticoids
* Subject is known to be HIV positive.
* Use of known inhibitors or inducers of cytochrome P450 3A (CYP3A) within two weeks prior to study drug administration
* Subject is contraindicated for the MRI examination
* Investigator considers subject unsuitable for any reason
* Subject has a history of drug or alcohol abuse within six months prior to screening
* Subject weighs more than 340 pounds (154 kg)
* Subject has had a liver transplant

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2009
Sample size
Target
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital - Renal Unit - Liverpool
Recruitment hospital [2] 0 0
Westmead Hospital - Dept. of Renal Medicine - Sydney
Recruitment hospital [3] 0 0
The Princess Alexandra Hospital - Nephrology Dept. - Wooloongabba
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Dept. of Nephrology - Parkville
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2145 - Sydney
Recruitment postcode(s) [3] 0 0
4102 - Wooloongabba
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
Nebraska
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
Czech Republic
State/province [17] 0 0
Brno
Country [18] 0 0
Czech Republic
State/province [18] 0 0
Pizen
Country [19] 0 0
Czech Republic
State/province [19] 0 0
Prague 4
Country [20] 0 0
Czech Republic
State/province [20] 0 0
Praha 2
Country [21] 0 0
Czech Republic
State/province [21] 0 0
Praha 6
Country [22] 0 0
Germany
State/province [22] 0 0
Coburg
Country [23] 0 0
Germany
State/province [23] 0 0
Dortmund
Country [24] 0 0
Germany
State/province [24] 0 0
Dusseldorf
Country [25] 0 0
Germany
State/province [25] 0 0
Nettetal
Country [26] 0 0
Germany
State/province [26] 0 0
Wurzburg
Country [27] 0 0
Greece
State/province [27] 0 0
Athens
Country [28] 0 0
Greece
State/province [28] 0 0
Thessaloniki
Country [29] 0 0
Italy
State/province [29] 0 0
Bologna
Country [30] 0 0
Italy
State/province [30] 0 0
Monza
Country [31] 0 0
Italy
State/province [31] 0 0
Pavia
Country [32] 0 0
Italy
State/province [32] 0 0
Trieste
Country [33] 0 0
Poland
State/province [33] 0 0
Katowice
Country [34] 0 0
Poland
State/province [34] 0 0
Lodz
Country [35] 0 0
Poland
State/province [35] 0 0
Szczecin
Country [36] 0 0
Poland
State/province [36] 0 0
Warszawa
Country [37] 0 0
Puerto Rico
State/province [37] 0 0
Caguas
Country [38] 0 0
Puerto Rico
State/province [38] 0 0
Rio Piedras
Country [39] 0 0
Romania
State/province [39] 0 0
Bucuresti
Country [40] 0 0
Romania
State/province [40] 0 0
Cluj-Napoca
Country [41] 0 0
Romania
State/province [41] 0 0
Iasi
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Moscow
Country [43] 0 0
Spain
State/province [43] 0 0
Cordoba
Country [44] 0 0
Spain
State/province [44] 0 0
Madrid
Country [45] 0 0
Spain
State/province [45] 0 0
Palma de Mallorca
Country [46] 0 0
Spain
State/province [46] 0 0
Pamplona
Country [47] 0 0
Spain
State/province [47] 0 0
Sevilla
Country [48] 0 0
Taiwan
State/province [48] 0 0
Hsin-Chuang City
Country [49] 0 0
Taiwan
State/province [49] 0 0
Taipei
Country [50] 0 0
Taiwan
State/province [50] 0 0
Taoyuan
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Coventry
Country [52] 0 0
United Kingdom
State/province [52] 0 0
London
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Abbott
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Massachusetts General Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Harvard University
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
To evaluate the effects of paricalcitol injection on cardiac structure and function over 48 weeks in subjects with Stage 5 Chronic Kidney Disease (CKD) receiving hemodialysis who have left ventricular hypertrophy (LVH).
Trial website
https://clinicaltrials.gov/study/NCT00616902
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Dennis Andress, MD
Address 0 0
Abbott
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00616902