Trial Outcomes & Findings for Zoledronic Acid Versus Alendronate for Prevention of Bone Loss After Organ Transplantation (NCT NCT00297830)
NCT ID: NCT00297830
Last Updated: 2018-08-16
Results Overview
BMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
111 participants
Primary outcome timeframe
Baseline, 12 months
Results posted on
2018-08-16
Participant Flow
Men and women, aged 20 to 70 yr, who had undergone heart or liver transplantation at CUMC were eligible. Of 495 patients transplanted between 3/2006 and 7/2009, 235 were ineligible. 149 patients declined or were not approached. 84 were randomized, 43 to alendronate and 41 to zoledronate. 27 were the reference group since they refused randomization.
Serum creatinine levels above 2.0 mg/dl, or enrollment in another clinical trial
Participant milestones
| Measure |
Active Zoledronic Acid and Placebo Alendronate
Group 1 will receive an infusion of active zoledronic acid 5 mg during the first 4 weeks after transplantation. Placebo alendronate 70 mg once weekly will be initiated at the same time as the first zoledronic acid infusion.
|
Placebo Zoledronic Acid and Active Alendronate
Group 2 will receive an infusion of placebo during the first 5 weeks after transplantation. Active alendronate 70 mg once weekly will be initiated at the same time as the placebo infusion.
|
Reference Group
The reference group included concurrently transplanted patients with T scores of -1.5 or greater.
|
|---|---|---|---|
|
Baseline
STARTED
|
41
|
43
|
27
|
|
Baseline
COMPLETED
|
41
|
43
|
27
|
|
Baseline
NOT COMPLETED
|
0
|
0
|
0
|
|
6 Month Visit
STARTED
|
41
|
43
|
27
|
|
6 Month Visit
COMPLETED
|
38
|
41
|
24
|
|
6 Month Visit
NOT COMPLETED
|
3
|
2
|
3
|
|
12 Month Visit
STARTED
|
38
|
41
|
24
|
|
12 Month Visit
COMPLETED
|
37
|
35
|
24
|
|
12 Month Visit
NOT COMPLETED
|
1
|
6
|
0
|
Reasons for withdrawal
| Measure |
Active Zoledronic Acid and Placebo Alendronate
Group 1 will receive an infusion of active zoledronic acid 5 mg during the first 4 weeks after transplantation. Placebo alendronate 70 mg once weekly will be initiated at the same time as the first zoledronic acid infusion.
|
Placebo Zoledronic Acid and Active Alendronate
Group 2 will receive an infusion of placebo during the first 5 weeks after transplantation. Active alendronate 70 mg once weekly will be initiated at the same time as the placebo infusion.
|
Reference Group
The reference group included concurrently transplanted patients with T scores of -1.5 or greater.
|
|---|---|---|---|
|
6 Month Visit
Death
|
1
|
0
|
2
|
|
6 Month Visit
Withdrawal by Subject
|
2
|
1
|
1
|
|
6 Month Visit
Adverse Event
|
0
|
1
|
0
|
|
12 Month Visit
Lost to Follow-up
|
1
|
0
|
0
|
|
12 Month Visit
Adverse Event
|
0
|
3
|
0
|
|
12 Month Visit
Withdrawal by Subject
|
0
|
3
|
0
|
Baseline Characteristics
Zoledronic Acid Versus Alendronate for Prevention of Bone Loss After Organ Transplantation
Baseline characteristics by cohort
| Measure |
Active Zoledronic Acid and Placebo Alendronate
n=41 Participants
Group 1 will receive an infusion of active zoledronic acid 5 mg during the first 4 weeks after transplantation. Placebo alendronate 70 mg once weekly will be initiated at the same time as the first zoledronic acid infusion.
|
Placebo Infusion and Active Alendronate
n=43 Participants
Group 2 will receive an infusion of placebo during the first 5 weeks after transplantation. Active alendronate 70 mg once weekly will be initiated at the same time as the placebo infusion.
|
Reference Group
n=27 Participants
The reference group included concurrently transplanted patients with T scores of -1.5 or greater.
|
Total
n=111 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
55 years
STANDARD_DEVIATION 8 • n=5 Participants
|
54 years
STANDARD_DEVIATION 10 • n=7 Participants
|
48 years
STANDARD_DEVIATION 15 • n=5 Participants
|
52.9 years
STANDARD_DEVIATION 11.1 • n=4 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
26 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
85 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
37 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
90 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline, 12 monthsBMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer.
Outcome measures
| Measure |
Active Zoledronic Acid and Placebo Alendronate
n=37 Participants
Group 1 will receive an infusion of active zoledronic acid 5 mg during the first 4 weeks after transplantation. Placebo alendronate 70 mg once weekly will be initiated at the same time as the first zoledronic acid infusion.
|
Placebo Zoledronic Acid and Active Alendronate
n=35 Participants
Group 2 will receive an infusion of placebo during the first 5 weeks after transplantation. Active alendronate 70 mg once weekly will be initiated at the same time as the placebo infusion.
|
Reference Group
n=24 Participants
The reference group included concurrently transplanted patients with T scores of -1.5 or greater.
|
|---|---|---|---|
|
Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 12 Months
|
0.39 percent change
Interval -0.64 to 1.42
|
-0.21 percent change
Interval -1.25 to 0.84
|
-2.2 percent change
Interval -3.6 to -0.7
|
SECONDARY outcome
Timeframe: Baseline, 12 monthsBMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer.
Outcome measures
| Measure |
Active Zoledronic Acid and Placebo Alendronate
n=37 Participants
Group 1 will receive an infusion of active zoledronic acid 5 mg during the first 4 weeks after transplantation. Placebo alendronate 70 mg once weekly will be initiated at the same time as the first zoledronic acid infusion.
|
Placebo Zoledronic Acid and Active Alendronate
n=35 Participants
Group 2 will receive an infusion of placebo during the first 5 weeks after transplantation. Active alendronate 70 mg once weekly will be initiated at the same time as the placebo infusion.
|
Reference Group
n=24 Participants
The reference group included concurrently transplanted patients with T scores of -1.5 or greater.
|
|---|---|---|---|
|
Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months
|
1.98 percent change
Interval 0.55 to 3.4
|
-0.45 percent change
Interval -1.88 to 0.99
|
-2.6 percent change
Interval -4.4 to -0.9
|
SECONDARY outcome
Timeframe: Baseline, 12 monthsBMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer.
Outcome measures
| Measure |
Active Zoledronic Acid and Placebo Alendronate
n=37 Participants
Group 1 will receive an infusion of active zoledronic acid 5 mg during the first 4 weeks after transplantation. Placebo alendronate 70 mg once weekly will be initiated at the same time as the first zoledronic acid infusion.
|
Placebo Zoledronic Acid and Active Alendronate
n=35 Participants
Group 2 will receive an infusion of placebo during the first 5 weeks after transplantation. Active alendronate 70 mg once weekly will be initiated at the same time as the placebo infusion.
|
Reference Group
n=24 Participants
The reference group included concurrently transplanted patients with T scores of -1.5 or greater.
|
|---|---|---|---|
|
Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 12 Months
|
0.28 percent change
Interval -1.16 to 1.71
|
-0.57 percent change
Interval -2.02 to 0.88
|
-3.3 percent change
Interval -4.8 to -1.8
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: Serum n-telopeplide percent change was not collected.
Outcome measures
Outcome data not reported
Adverse Events
Active Zoledronic Acid and Placebo Alendronate
Serious events: 21 serious events
Other events: 14 other events
Deaths: 0 deaths
Placebo Infusion and Active Alendronate
Serious events: 14 serious events
Other events: 11 other events
Deaths: 0 deaths
Reference Group
Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Active Zoledronic Acid and Placebo Alendronate
n=41 participants at risk
Group 1 will receive an infusion of active zoledronic acid 5 mg during the first 4 weeks after transplantation. Placebo alendronate 70 mg once weekly will be initiated at the same time as the first zoledronic acid infusion.
|
Placebo Infusion and Active Alendronate
n=43 participants at risk
Group 2 will receive an infusion of placebo during the first 5 weeks after transplantation. Active alendronate 70 mg once weekly will be initiated at the same time as the placebo infusion.https://register.clinicaltrials.gov/prs/html/results\_definitions.html#Result\_ParticipantFlow\_Period\_title
|
Reference Group
n=27 participants at risk
The reference group included concurrently transplanted patients with T scores of -1.5 or greater.
|
|---|---|---|---|
|
General disorders
Death
|
2.4%
1/41 • Number of events 1 • 1 year
|
0.00%
0/43 • 1 year
|
7.4%
2/27 • Number of events 2 • 1 year
|
|
General disorders
Hospitalization
|
48.8%
20/41 • Number of events 20 • 1 year
|
32.6%
14/43 • Number of events 14 • 1 year
|
0.00%
0/27 • 1 year
|
Other adverse events
| Measure |
Active Zoledronic Acid and Placebo Alendronate
n=41 participants at risk
Group 1 will receive an infusion of active zoledronic acid 5 mg during the first 4 weeks after transplantation. Placebo alendronate 70 mg once weekly will be initiated at the same time as the first zoledronic acid infusion.
|
Placebo Infusion and Active Alendronate
n=43 participants at risk
Group 2 will receive an infusion of placebo during the first 5 weeks after transplantation. Active alendronate 70 mg once weekly will be initiated at the same time as the placebo infusion.https://register.clinicaltrials.gov/prs/html/results\_definitions.html#Result\_ParticipantFlow\_Period\_title
|
Reference Group
n=27 participants at risk
The reference group included concurrently transplanted patients with T scores of -1.5 or greater.
|
|---|---|---|---|
|
Infections and infestations
Infection
|
34.1%
14/41 • Number of events 14 • 1 year
|
25.6%
11/43 • Number of events 11 • 1 year
|
0.00%
0/27 • 1 year
|
|
General disorders
Rejection
|
9.8%
4/41 • Number of events 4 • 1 year
|
4.7%
2/43 • Number of events 2 • 1 year
|
0.00%
0/27 • 1 year
|
|
General disorders
Flu-like symptoms after zoledronate or matching placebo
|
4.9%
2/41 • Number of events 2 • 1 year
|
2.3%
1/43 • Number of events 1 • 1 year
|
0.00%
0/27 • 1 year
|
|
Endocrine disorders
Hypocalcemia
|
9.8%
4/41 • Number of events 4 • 1 year
|
11.6%
5/43 • Number of events 5 • 1 year
|
0.00%
0/27 • 1 year
|
|
Endocrine disorders
Serum Calcium > 2.0 mg/dL
|
2.4%
1/41 • Number of events 1 • 1 year
|
16.3%
7/43 • Number of events 7 • 1 year
|
0.00%
0/27 • 1 year
|
|
Cardiac disorders
Atrial fibrillation
|
4.9%
2/41 • Number of events 2 • 1 year
|
0.00%
0/43 • 1 year
|
0.00%
0/27 • 1 year
|
|
General disorders
Abdominal Pain
|
2.4%
1/41 • Number of events 1 • 1 year
|
4.7%
2/43 • Number of events 2 • 1 year
|
0.00%
0/27 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
4.9%
2/41 • Number of events 2 • 1 year
|
2.3%
1/43 • Number of events 1 • 1 year
|
0.00%
0/27 • 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place