Trial Outcomes & Findings for Treatment With Zoledronic Acid Subsequent to Denosumab in Osteoporosis (NCT NCT03087851)
NCT ID: NCT03087851
Last Updated: 2021-02-21
Results Overview
Change in lumbar spine BMD from baseline to 6 months after the zoledronic acid infusion.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
61 participants
Primary outcome timeframe
baseline to 6 months after the zoledronic acid infusion
Results posted on
2021-02-21
Participant Flow
We recruited participants from the Department of Endocrinology, Aarhus University Hospital, Denmark and via advertisements in newspapers and online. The Danish Health Data Authority provided two data extractions, with information on patients living in the Central Region of Denmark, who had redeemed a minimum of 5 prescriptions for denosumab (DMAB) within the last 3 years.
Participant milestones
| Measure |
6-month Group
Zoledronate: administrated at baseline.
Zoledronate re-adminisrated:
If p-C-terminal telopeptide of type 1 collagen (p-CTX) increases above 1.26 ug/l or bone mineral density (BMD) decreases more than 5% at any site.
|
9-months Group
Zoledronate: administrated depending on increase in p-CTX (above 1.26 ug/l) or the occurrence of an osteoporotic clinical vertebral or hip fracture, but no later than at month 3.
Zoledronate re-administrated:
If p-CTX increases above 1.26 ug/l or BMD decreases more than 5% at any site.
|
Observation Group
Zoledronate: administrated depending on increase in p-CTX (above 1.26 ug/l), decrease in BMD (more than 5%), or the occurrence of an osteoporotic clinical vertebral or hip fracture, but no later than at month 6.
Zoledronate re-administrated:
If p-CTX increases above 1.26 ug/l or BMD decreases more than 5% at any site.
|
|---|---|---|---|
|
Overall Study
STARTED
|
20
|
20
|
21
|
|
Overall Study
COMPLETED
|
20
|
19
|
19
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
2
|
Reasons for withdrawal
| Measure |
6-month Group
Zoledronate: administrated at baseline.
Zoledronate re-adminisrated:
If p-C-terminal telopeptide of type 1 collagen (p-CTX) increases above 1.26 ug/l or bone mineral density (BMD) decreases more than 5% at any site.
|
9-months Group
Zoledronate: administrated depending on increase in p-CTX (above 1.26 ug/l) or the occurrence of an osteoporotic clinical vertebral or hip fracture, but no later than at month 3.
Zoledronate re-administrated:
If p-CTX increases above 1.26 ug/l or BMD decreases more than 5% at any site.
|
Observation Group
Zoledronate: administrated depending on increase in p-CTX (above 1.26 ug/l), decrease in BMD (more than 5%), or the occurrence of an osteoporotic clinical vertebral or hip fracture, but no later than at month 6.
Zoledronate re-administrated:
If p-CTX increases above 1.26 ug/l or BMD decreases more than 5% at any site.
|
|---|---|---|---|
|
Overall Study
Withdraw on medical grounds
|
0
|
1
|
2
|
Baseline Characteristics
Treatment With Zoledronic Acid Subsequent to Denosumab in Osteoporosis
Baseline characteristics by cohort
| Measure |
6-month Group
n=20 Participants
Treated with zoledronate 5 mg
|
9-months Group
n=20 Participants
Treated with zoledronate 5 mg
|
Observation Group
n=21 Participants
Treated with zoledronate 5 mg
|
Total
n=61 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
27 Participants
n=7 Participants
|
|
Age, Categorical
>=65 years
|
12 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
34 Participants
n=7 Participants
|
|
Age, Continuous
|
68 years
STANDARD_DEVIATION 8 • n=99 Participants
|
65 years
STANDARD_DEVIATION 7 • n=107 Participants
|
69 years
STANDARD_DEVIATION 9 • n=206 Participants
|
68 years
STANDARD_DEVIATION 8 • n=7 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
19 Participants
n=206 Participants
|
54 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
20 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
21 Participants
n=206 Participants
|
61 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Lumbar spine BMD
|
0,880 g/cm^2
STANDARD_DEVIATION 0.055 • n=99 Participants
|
0,878 g/cm^2
STANDARD_DEVIATION 0,063 • n=107 Participants
|
0,871 g/cm^2
STANDARD_DEVIATION 0,089 • n=206 Participants
|
0,876 g/cm^2
STANDARD_DEVIATION 0,069 • n=7 Participants
|
PRIMARY outcome
Timeframe: baseline to 6 months after the zoledronic acid infusionPopulation: Change in lumbar spine BMD from baseline to 6 months after the zoledronic acid infusion.
Change in lumbar spine BMD from baseline to 6 months after the zoledronic acid infusion.
Outcome measures
| Measure |
6-month Group
n=20 Participants
n=20
|
9-months Group
n=20 Participants
n=20
|
Observation Group
n=21 Participants
n=21
|
|---|---|---|---|
|
Change in Lumbar Spine BMD From Baseline to 6 Months After the Zoledronic Acid Infusion.
|
-2.1 percentage change
Standard Error 0.9
|
-4.3 percentage change
Standard Error 1.1
|
-3.0 percentage change
Standard Error 1.1
|
PRIMARY outcome
Timeframe: 2 years after the first ZOL treatmentPopulation: Number of Participants Who Fail to Maintain lumbar spine BMD from baseline to 24 months after the first ZOL
Failure is defined as ≥ 3 % BMD loss at the lumbar spine
Outcome measures
| Measure |
6-month Group
n=20 Participants
n=20
|
9-months Group
n=20 Participants
n=20
|
Observation Group
n=21 Participants
n=21
|
|---|---|---|---|
|
Number of Participants Who Fail to Maintain BMD
|
10 participants
|
5 participants
|
6 participants
|
SECONDARY outcome
Timeframe: from baseline to one year after the zoledronic acid infusionPopulation: Changes in lumbar spine BMD from baseline to one year after the zoledronic acid infusion.
Changes in lumbar spine BMD from baseline to one year after the zoledronic acid infusion.
Outcome measures
| Measure |
6-month Group
n=20 Participants
n=20
|
9-months Group
n=20 Participants
n=20
|
Observation Group
n=21 Participants
n=21
|
|---|---|---|---|
|
Changes in BMD From Baseline to One Year After the Zoledronic Acid Infusion.
|
-4.8 percentage change
Standard Error 0.7
|
-4.1 percentage change
Standard Error 1.1
|
-4.7 percentage change
Standard Error 1.2
|
SECONDARY outcome
Timeframe: from baseline to two years after the zoledronic acid infusion.Population: Changes in lumbar spine BMD from baseline to two years after the zoledronic acid infusion.
Changes in lumbar spine BMD from baseline to two years after the zoledronic acid infusion.
Outcome measures
| Measure |
6-month Group
n=20 Participants
n=20
|
9-months Group
n=20 Participants
n=20
|
Observation Group
n=21 Participants
n=21
|
|---|---|---|---|
|
Changes in BMD From Baseline to Two Years After the Zoledronic Acid Infusion.
|
-4.0 percentage change
Standard Error 0.8
|
-4.1 percentage change
Standard Error 0.8
|
-4.3 percentage change
Standard Error 1.5
|
SECONDARY outcome
Timeframe: from baseline to one year after the zoledronic acid infusion.Population: Changes in cortical porosity at the radius from baseline to one year after the zoledronic acid infusion.
Changes in cortical porosity measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) scan at the radius and tibia from baseline to one year after the zoledronic acid infusion.
Outcome measures
| Measure |
6-month Group
n=20 Participants
n=20
|
9-months Group
n=20 Participants
n=20
|
Observation Group
n=21 Participants
n=21
|
|---|---|---|---|
|
Changes in Cortical Porosity Measured by High-resolution Peripheral Quantitative Computed Tomography (HR-pQCT) Scan at the Radius and Tibia From Baseline to One Year After the Zoledronic Acid Infusion.
|
-2.5 percentage change
Standard Error 7.4
|
-1.6 percentage change
Standard Error 6.7
|
-4.2 percentage change
Standard Error 7.2
|
SECONDARY outcome
Timeframe: from baseline to six months after the zoledronic acid infusion.Population: Changes in p-CTX from baseline to six months after the zoledronic acid infusion.
Changes in p-CTX from baseline to six months after the zoledronic acid infusion.
Outcome measures
| Measure |
6-month Group
n=20 Participants
n=20
|
9-months Group
n=20 Participants
n=20
|
Observation Group
n=21 Participants
n=21
|
|---|---|---|---|
|
Changes in p-CTX From Baseline to Six Months After the Zoledronic Acid Infusion.
|
0.60 ug/l
Standard Deviation 0.35
|
0.47 ug/l
Standard Deviation 0.24
|
0.47 ug/l
Standard Deviation 0.20
|
SECONDARY outcome
Timeframe: from baseline to 12 months after the zoledronic acid infusion.Population: Changes in p-CTX from baseline to 12 months after the zoledronic acid infusion.
Changes in p-CTX from baseline to 12 months after the zoledronic acid infusion.
Outcome measures
| Measure |
6-month Group
n=20 Participants
n=20
|
9-months Group
n=20 Participants
n=20
|
Observation Group
n=21 Participants
n=21
|
|---|---|---|---|
|
Changes in p-CTX From Baseline to 12 Months After the Zoledronic Acid Infusion.
|
0.58 ug/l
Standard Deviation 0.23
|
0.40 ug/l
Standard Deviation 0.20
|
0.49 ug/l
Standard Deviation 0.21
|
SECONDARY outcome
Timeframe: one and two years after the zoledronic acid infusion.Population: Morphometric vertebral fractures assessed by vertebral fracture assessment (VFA) two years after the zoledronic acid infusion.
Morphometric vertebral fractures assessed by vertebral fracture assessment (VFA) one and two years after the zoledronic acid infusion.
Outcome measures
| Measure |
6-month Group
n=20 Participants
n=20
|
9-months Group
n=20 Participants
n=20
|
Observation Group
n=21 Participants
n=21
|
|---|---|---|---|
|
Morphometric Vertebral Fractures Assessed by Vertebral Fracture Assessment (VFA) One and Two Years After the Zoledronic Acid Infusion.
|
0 participants
|
2 participants
|
0 participants
|
Adverse Events
6-month Group
Serious events: 0 serious events
Other events: 18 other events
Deaths: 0 deaths
9-months Group
Serious events: 1 serious events
Other events: 18 other events
Deaths: 0 deaths
Observation Group
Serious events: 4 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
6-month Group
n=20 participants at risk
Zoledronate: administrated at baseline.
Zoledronate re-administrated: If s-CTX increases above 1.26 ug/l or BMD decreases more than 5% at any site.
|
9-months Group
n=20 participants at risk
Zoledronate: administrated depending on increase in s-CTX (above 1.26 ug/l) or the occurrence of an osteoporotic clinical vertebral or hip fracture, but no later than at month 3.
Zoledronate re-administrated: If s-CTX increases above 1.26 ug/l or BMD decreases more than 5% at any site.
|
Observation Group
n=21 participants at risk
Zoledronate: administrated depending on increase in s-CTX (above 1.26 ug/l), decrease in BMD (more than 5% at any site), or the occurrence of an osteoporotic clinical vertebral or hip fracture, but no later than at month 6.
Zoledronate re-administrated: If s-CTX increases above 1.26 ug/l or BMD decreases more than 5% at any site.
|
|---|---|---|---|
|
Investigations
Cancer
|
0.00%
0/20 • 2 - 2.5 years
|
5.0%
1/20 • Number of events 1 • 2 - 2.5 years
|
19.0%
4/21 • Number of events 4 • 2 - 2.5 years
|
Other adverse events
| Measure |
6-month Group
n=20 participants at risk
Zoledronate: administrated at baseline.
Zoledronate re-administrated: If s-CTX increases above 1.26 ug/l or BMD decreases more than 5% at any site.
|
9-months Group
n=20 participants at risk
Zoledronate: administrated depending on increase in s-CTX (above 1.26 ug/l) or the occurrence of an osteoporotic clinical vertebral or hip fracture, but no later than at month 3.
Zoledronate re-administrated: If s-CTX increases above 1.26 ug/l or BMD decreases more than 5% at any site.
|
Observation Group
n=21 participants at risk
Zoledronate: administrated depending on increase in s-CTX (above 1.26 ug/l), decrease in BMD (more than 5% at any site), or the occurrence of an osteoporotic clinical vertebral or hip fracture, but no later than at month 6.
Zoledronate re-administrated: If s-CTX increases above 1.26 ug/l or BMD decreases more than 5% at any site.
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Flu-like symptoms after ZOL treatment
|
65.0%
13/20 • Number of events 13 • 2 - 2.5 years
|
40.0%
8/20 • Number of events 8 • 2 - 2.5 years
|
76.2%
16/21 • Number of events 16 • 2 - 2.5 years
|
|
Infections and infestations
Infection (unspecified) + Musculoskeletal symptoms
|
65.0%
13/20 • Number of events 13 • 2 - 2.5 years
|
90.0%
18/20 • Number of events 18 • 2 - 2.5 years
|
71.4%
15/21 • Number of events 15 • 2 - 2.5 years
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
10.0%
2/20 • Number of events 2 • 2 - 2.5 years
|
10.0%
2/20 • Number of events 2 • 2 - 2.5 years
|
9.5%
2/21 • Number of events 2 • 2 - 2.5 years
|
Additional Information
MD Anne Sophie Sølling
Dep. of Endocrinology and Internal Medicine, Aarhus University Hospital
Phone: 78 45 54 75
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place