Trial Outcomes & Findings for The PRIMO II Study: Paricalcitol Injection Benefits in Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease (CKD) Stage 5 (NCT NCT00616902)
NCT ID: NCT00616902
Last Updated: 2012-01-20
Results Overview
Change from Baseline in left ventricular mass index (LVMI) over 48 weeks measured by cardiac MRI. The effects of paricalcitol injection on progression or regression of left ventricular hypertrophy (LVH) in participants with Stage 5 chronic kidney disease (CKD) on hemodialysis (HD) compared to placebo. Left Ventricular Mass is normalized to the participant's height by the following equation to obtain LVMI: LVM (g) divided by height (m)2.7. The primary comparison was between the 4 mcg paricalcitol injection and the placebo treatment groups in the change from baseline to Week 48.
TERMINATED
PHASE3
12 participants
Baseline, 24 Weeks, and 48 Weeks/Early Termination
2012-01-20
Participant Flow
A total of 220 participants were to be randomized in a 1:1 ratio to each treatment group to receive paricalcitol injection or placebo at 75 US and ex-US sites. A stratified randomization scheme was used to ensure balance among treatment groups with respect to country, sex, and baseline Renin Angiotensin-Aldosterone System (RAAS) inhibitor use.
The Screening Period consisted of 3 visits and occurred within 6 weeks prior to participant randomization and enrollment into the Treatment Period of the study. For enrollment, all screening labs and echocardiogram requirements had to be met. Also, a technically adequate cardiac MRI had to be obtained for participant to be randomized into study.
Participant milestones
| Measure |
Paricalcitol Injection 4 Mcg/mL
Paricalcitol Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
Placebo Injection 4 Mcg/mL
Placebo Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
6
|
Reasons for withdrawal
| Measure |
Paricalcitol Injection 4 Mcg/mL
Paricalcitol Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
Placebo Injection 4 Mcg/mL
Placebo Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
|---|---|---|
|
Overall Study
Termination of study
|
6
|
6
|
Baseline Characteristics
The PRIMO II Study: Paricalcitol Injection Benefits in Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease (CKD) Stage 5
Baseline characteristics by cohort
| Measure |
Paricalcitol Injection 4 Mcg/mL
n=6 Participants
Paricalcitol Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
Placebo Injection 4 Mcg/mL
n=6 Participants
Placebo Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
< 40 years
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Age, Customized
40 - < 60 years
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Age, Customized
>= 60 years
|
2 participants
n=5 Participants
|
4 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Age Continuous
|
54.5 years
STANDARD_DEVIATION 16.01 • n=5 Participants
|
58.8 years
STANDARD_DEVIATION 7.05 • n=7 Participants
|
56.7 years
STANDARD_DEVIATION 12.01 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, 24 Weeks, and 48 Weeks/Early TerminationPopulation: The Intent-To-Treat (ITT) population - all randomized participants who were administered at least one dose of study drug and the Evaluable population (a subset of ITT population and consists of those participants who have completed Week 24 visit). None of the participants completed 24 or 48 weeks.
Change from Baseline in left ventricular mass index (LVMI) over 48 weeks measured by cardiac MRI. The effects of paricalcitol injection on progression or regression of left ventricular hypertrophy (LVH) in participants with Stage 5 chronic kidney disease (CKD) on hemodialysis (HD) compared to placebo. Left Ventricular Mass is normalized to the participant's height by the following equation to obtain LVMI: LVM (g) divided by height (m)2.7. The primary comparison was between the 4 mcg paricalcitol injection and the placebo treatment groups in the change from baseline to Week 48.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, 24 Weeks, and 48 Weeks/Early TerminationPopulation: The Intent-To-Treat (ITT) population - all randomized participants who were administered at least one dose of study drug. None of the participants completed 24 or 48 weeks.
Mitral Annular relaxation velocity is a measure of diastolic heart function.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, 24 Weeks, and 48 Weeks/Early TerminationPopulation: The Intent-To-Treat (ITT) population - all randomized participants who were administered at least one dose of study drug. None of the participants completed 24 or 48 weeks.
Isovolumetric relaxation time is a measure of diastolic heart function.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 24, and Week 48/Early TerminationPopulation: The Intent-To-Treat (ITT) population - all randomized participants who were administered at least one dose of study drug. None of the participants completed 24 or 48 weeks.
The ratio of peak E-wave velocity to lateral e-wave velocity is a measure of diastolic heart function.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, 24 Weeks, and 48 Weeks/Early TerminationPopulation: The Intent-To-Treat (ITT) population - all randomized participants who were administered at least one dose of study drug. None of the participants completed 24 or 48 weeks.
E-wave deceleration time is a measure of diastolic heart function.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)Population: The Intent-To-Treat (ITT) population - all randomized participants administered at least one dose of study drug. Results reported are from the early termination visit analysis for the subjects who terminated prematurely. None of the participants completed 24 or 48 weeks.
Plasma T3 is a circulating hormone that may have an effect on diastolic heart function and its level may be affected by treatment with paricalcitol. The study was terminated early (prior to any subject reaching Week 24). The values are for Baseline and Early Termination only. Each of the 12 randomized subjects terminated at different study weeks; therefore Early Termination cannot be defined as a specific week and varies for different subjects. Of the 12 subjects, 11 had early termination visits and 1 didn't. The final visit week range is 4-16.
Outcome measures
| Measure |
Paricalcitol Injection 4 Mcg/mL
n=5 Participants
Paricalcitol Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
Placebo Injection 4 Mcg/mL
n=6 Participants
Placebo Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
|---|---|---|
|
Change From Baseline in Biological Marker Triiodothyronine (T3).
|
0.005 nmol/L
Standard Deviation 0.5455
|
-0.152 nmol/L
Standard Deviation 0.3640
|
SECONDARY outcome
Timeframe: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)Population: The Intent-To-Treat (ITT) population - all randomized participants administered at least one dose of study drug. Results reported are from the early termination visit analysis for the subjects who terminated prematurely. None of the participants completed 24 or 48 weeks.
Plasma troponin-t is a marker of heart damage and and its level may be affected by treatment with paricalcitol. The study was terminated early (prior to any subject reaching Week 24). The values are for Baseline and Early Termination only. Each of the 12 randomized subjects terminated at different study weeks; therefore Early Termination cannot be defined as a specific week and varies for different subjects. Of the 12 subjects, 11 had early termination visits and 1 didn't. The final visit week range is 4-16.
Outcome measures
| Measure |
Paricalcitol Injection 4 Mcg/mL
n=5 Participants
Paricalcitol Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
Placebo Injection 4 Mcg/mL
n=6 Participants
Placebo Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
|---|---|---|
|
Change From Baseline in Biological Marker Plasma Troponin-T Over 48 Weeks
|
-0.014 mcg/L
Standard Deviation 0.0195
|
-0.007 mcg/L
Standard Deviation 0.0175
|
SECONDARY outcome
Timeframe: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)Population: The Intent-To-Treat (ITT) population - all randomized participants administered at least one dose of study drug. Results reported are from the early termination visit analysis for the subjects who terminated prematurely. None of the participants completed 24 or 48 weeks.
Plasma IL-6 is a biomarker of inflammation that may have an effect on heart function and its level may be affected by treatment with paricalcitol. The study was terminated early (prior to any subject reaching Week 24). The values are for Baseline and Early Termination only. Each of the 12 randomized subjects terminated at different study weeks; therefore Early Termination cannot be defined as a specific week and varies for different subjects. Of the 12 subjects, 11 had early termination visits and 1 didn't. The final visit week range is 4-16.
Outcome measures
| Measure |
Paricalcitol Injection 4 Mcg/mL
n=5 Participants
Paricalcitol Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
Placebo Injection 4 Mcg/mL
n=6 Participants
Placebo Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
|---|---|---|
|
Change From Baseline in Biological Marker Plasma Interleukin-6 (IL-6) Over 48 Weeks
|
-0.200 cm/sec
Standard Deviation 1.0954
|
0.333 cm/sec
Standard Deviation 3.7771
|
SECONDARY outcome
Timeframe: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)Population: The Intent-To-Treat (ITT) population - all randomized participants administered at least one dose of study drug. Results reported are from the early termination visit analysis for the subjects who terminated prematurely. None of the participants completed 24 or 48 weeks.
Plasma high sensitivity CRP is a biomarker of inflammation that may have an effect on heart function and its level may be affected by treatment with paricalcitol. The study was terminated early (prior to any subject reaching Week 24). The values are for Baseline and Early Termination only. Each of the 12 randomized subjects terminated at different study weeks; therefore Early Termination cannot be defined as a specific week and varies for different subjects. Of the 12 subjects, 11 had early termination visits and 1 didn't. The final visit week range is 4-16.
Outcome measures
| Measure |
Paricalcitol Injection 4 Mcg/mL
n=5 Participants
Paricalcitol Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
Placebo Injection 4 Mcg/mL
n=6 Participants
Placebo Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
|---|---|---|
|
Change From Baseline in Biological Marker Plasma High Sensitivity C-reactive Protein (hsCRP) Over 48 Weeks
|
1.104 mg/L
Standard Deviation 1.9361
|
-0.762 mg/L
Standard Deviation 5.0013
|
SECONDARY outcome
Timeframe: Baseline and Early Termination Visit (4 Weeks, 5 Weeks, 7 Weeks, 8 Weeks, 14 Weeks, and 16 Weeks)Population: The Intent-To-Treat (ITT) population - all randomized participants administered at least one dose of study drug. Results reported are from the early termination visit analysis for the subjects who terminated prematurely. None of the participants completed 24 or 48 weeks.
Plasma BNP is a product from the heart that becomes elevated with an enlarged heart and its level may be affected by treatment with paricalcitol. The study was terminated early (prior to any subject reaching Week 24). The values are for Baseline and Early Termination only. Each of the 12 randomized subjects terminated at different study weeks; therefore Early Termination cannot be defined as a specific week and varies for different subjects. Of the 12 subjects, 11 had early termination visits and 1 didn't. The final visit week range is 4-16.
Outcome measures
| Measure |
Paricalcitol Injection 4 Mcg/mL
n=5 Participants
Paricalcitol Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
Placebo Injection 4 Mcg/mL
n=6 Participants
Placebo Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
|---|---|---|
|
Change From Baseline in Biological Marker Plasma B-Type Natriuretic Peptide (BNP)
|
-134.200 ng/L
Standard Deviation 119.6963
|
572.800 ng/L
Standard Deviation 903.6101
|
Adverse Events
Paricalcitol Injection 4 Mcg/mL
Placebo Injection 4 Mcg/mL
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Paricalcitol Injection 4 Mcg/mL
n=6 participants at risk
Paricalcitol Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
Placebo Injection 4 Mcg/mL
n=6 participants at risk
Placebo Injection 4 mcg/mL given intravenously 3 times per week during dialysis.
|
|---|---|---|
|
General disorders
Chills
|
16.7%
1/6 • 48 weeks
|
0.00%
0/6 • 48 weeks
|
|
Nervous system disorders
Headache
|
16.7%
1/6 • 48 weeks
|
0.00%
0/6 • 48 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
1/6 • 48 weeks
|
0.00%
0/6 • 48 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
16.7%
1/6 • 48 weeks
|
0.00%
0/6 • 48 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
16.7%
1/6 • 48 weeks
|
0.00%
0/6 • 48 weeks
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
16.7%
1/6 • 48 weeks
|
0.00%
0/6 • 48 weeks
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
16.7%
1/6 • 48 weeks
|
0.00%
0/6 • 48 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
1/6 • 48 weeks
|
0.00%
0/6 • 48 weeks
|
|
Ear and labyrinth disorders
Ear pruritus
|
16.7%
1/6 • 48 weeks
|
0.00%
0/6 • 48 weeks
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/6 • 48 weeks
|
16.7%
1/6 • 48 weeks
|
|
Gastrointestinal disorders
vomiting
|
0.00%
0/6 • 48 weeks
|
16.7%
1/6 • 48 weeks
|
|
Musculoskeletal and connective tissue disorders
musculoskeletal pain
|
0.00%
0/6 • 48 weeks
|
16.7%
1/6 • 48 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
0.00%
0/6 • 48 weeks
|
16.7%
1/6 • 48 weeks
|
|
Vascular disorders
Hypertension
|
0.00%
0/6 • 48 weeks
|
16.7%
1/6 • 48 weeks
|
Additional Information
Global Medical Services
Abbott
Results disclosure agreements
- Principal investigator is a sponsor employee Abbott requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. Abbott requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Abbott needs to secure patent or proprietary protection.
- Publication restrictions are in place
Restriction type: OTHER