Trial Outcomes & Findings for Zoledronic Acid in Acute Spinal Cord Injury (NCT NCT01642901)
NCT ID: NCT01642901
Last Updated: 2023-05-23
Results Overview
Percent change in areal bone mineral density (aBMD) assessed by dual energy X-ray absorptiometry (DXA) at 4 months compared to baseline. This will compare aBMD at the hip.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
16 participants
Primary outcome timeframe
4 months
Results posted on
2023-05-23
Participant Flow
Participants were recruited from two comprehensive acute inpatient rehabilitation facilities between September 2012 and March 2017.
Prior to day 10 post injury, investigators obtained serum calcium, intact parathyroid hormone and serum 25-hydroxy (25-OH) vitamin D levels to determine further eligibility. Participants with vitamin D deficiency were allowed to receive supplementation to raise their level above 13 ng/mL in order to participate. One participant who was consented was subsequently found to have facial fractures and was withdrawn prior to randomization.
Participant milestones
| Measure |
Zoledronic Acid 5 mg IV Infusion
Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
Zoledronic acid: 5 mg zoledronic acid infused intravenously over two hours (2.5mg per hour), given only once, within 21 days of acute traumatic spinal cord injury.
|
Normal Saline 0.9%
Infusion of normal saline of equivalent volume to reconstituted zoledronic acid, given only once and run over 2 hours, to occur within 21 days of acute traumatic spinal cord injury.
normal saline 0.9%: Infusion of equivalent volume of 0.9% normal saline to that of the reconstituted zoledronic acid, given only once over two hours, occurring within 21 days of acute traumatic spinal cord injury
|
|---|---|---|
|
Intervention
STARTED
|
10
|
5
|
|
Intervention
COMPLETED
|
10
|
5
|
|
Intervention
NOT COMPLETED
|
0
|
0
|
|
4-month Follow-up
STARTED
|
10
|
5
|
|
4-month Follow-up
COMPLETED
|
10
|
5
|
|
4-month Follow-up
NOT COMPLETED
|
0
|
0
|
|
12-month Follow-up
STARTED
|
10
|
5
|
|
12-month Follow-up
COMPLETED
|
9
|
5
|
|
12-month Follow-up
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Zoledronic Acid 5 mg IV Infusion
Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
Zoledronic acid: 5 mg zoledronic acid infused intravenously over two hours (2.5mg per hour), given only once, within 21 days of acute traumatic spinal cord injury.
|
Normal Saline 0.9%
Infusion of normal saline of equivalent volume to reconstituted zoledronic acid, given only once and run over 2 hours, to occur within 21 days of acute traumatic spinal cord injury.
normal saline 0.9%: Infusion of equivalent volume of 0.9% normal saline to that of the reconstituted zoledronic acid, given only once over two hours, occurring within 21 days of acute traumatic spinal cord injury
|
|---|---|---|
|
12-month Follow-up
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Zoledronic Acid in Acute Spinal Cord Injury
Baseline characteristics by cohort
| Measure |
Zoledronic Acid 5 mg IV Infusion
n=10 Participants
Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
Zoledronic acid: 5 mg zoledronic acid infused intravenously over two hours (2.5mg per hour), given only once, within 21 days of acute traumatic spinal cord injury.
|
Normal Saline 0.9%
n=5 Participants
Infusion of normal saline of equivalent volume to reconstituted zoledronic acid, given only once and run over 2 hours, to occur within 21 days of acute traumatic spinal cord injury.
normal saline 0.9%: Infusion of equivalent volume of 0.9% normal saline to that of the reconstituted zoledronic acid, given only once over two hours, occurring within 21 days of acute traumatic spinal cord injury
|
Total
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
35.9 years
STANDARD_DEVIATION 12.6 • n=99 Participants
|
30.8 years
STANDARD_DEVIATION 9.9 • n=107 Participants
|
34.2 years
STANDARD_DEVIATION 11.7 • n=206 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
6 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=99 Participants
|
5 participants
n=107 Participants
|
15 participants
n=206 Participants
|
|
Total proximal femur areal bone mineral density (aBMD)
|
0.98 g/cm^2
STANDARD_DEVIATION 0.076 • n=99 Participants
|
1.09 g/cm^2
STANDARD_DEVIATION 0.138 • n=107 Participants
|
1.02 g/cm^2
STANDARD_DEVIATION 0.108 • n=206 Participants
|
|
Intertrochanteric femur aBMD
|
1.15 g/cm^2
STANDARD_DEVIATION 0.094 • n=99 Participants
|
1.28 g/cm^2
STANDARD_DEVIATION 0.147 • n=107 Participants
|
1.19 g/cm^2
STANDARD_DEVIATION 0.126 • n=206 Participants
|
|
Femoral neck aBMD
|
0.86 g/cm^2
STANDARD_DEVIATION 0.078 • n=99 Participants
|
0.98 g/cm^2
STANDARD_DEVIATION 0.178 • n=107 Participants
|
0.90 g/cm^2
STANDARD_DEVIATION 0.127 • n=206 Participants
|
|
Distal femur aBMD
|
0.88 g/cm^2
STANDARD_DEVIATION 0.092 • n=99 Participants
|
1.01 g/cm^2
STANDARD_DEVIATION 0.128 • n=107 Participants
|
0.924 g/cm^2
STANDARD_DEVIATION 0.118 • n=206 Participants
|
|
Proximal tibia aBMD
|
0.94 g/cm^2
STANDARD_DEVIATION 0.138 • n=99 Participants
|
1.11 g/cm^2
STANDARD_DEVIATION 0.217 • n=107 Participants
|
1.00 g/cm^2
STANDARD_DEVIATION 0.180 • n=206 Participants
|
|
serum C-telopeptide (CTX)
|
1255 pg/ml
STANDARD_DEVIATION 704 • n=99 Participants
|
980 pg/ml
STANDARD_DEVIATION 439 • n=107 Participants
|
1163 pg/ml
STANDARD_DEVIATION 626 • n=206 Participants
|
|
procollagen N-1 terminal propeptide (P1NP)
|
67.9 mcg/L
STANDARD_DEVIATION 37.9 • n=99 Participants
|
52.8 mcg/L
STANDARD_DEVIATION 9.50 • n=107 Participants
|
62.9 mcg/L
STANDARD_DEVIATION 31.7 • n=206 Participants
|
PRIMARY outcome
Timeframe: 4 monthsPercent change in areal bone mineral density (aBMD) assessed by dual energy X-ray absorptiometry (DXA) at 4 months compared to baseline. This will compare aBMD at the hip.
Outcome measures
| Measure |
Zoledronic Acid 5 mg IV Infusion
n=10 Participants
Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
Zoledronic acid: 5 mg zoledronic acid infused intravenously over two hours (2.5mg per hour), given only once, within 21 days of acute traumatic spinal cord injury.
|
Normal Saline 0.9%
n=5 Participants
Infusion of normal saline of equivalent volume to reconstituted zoledronic acid, given only once and run over 2 hours, to occur within 21 days of acute traumatic spinal cord injury.
normal saline 0.9%: Infusion of equivalent volume of 0.9% normal saline to that of the reconstituted zoledronic acid, given only once over two hours, occurring within 21 days of acute traumatic spinal cord injury
|
|---|---|---|
|
Change in Areal Bone Mineral Density at Hip
Total proximal femur
|
0.92 percentage change
Standard Deviation 7.14
|
-12.0 percentage change
Standard Deviation 7.50
|
|
Change in Areal Bone Mineral Density at Hip
Intertrochanteric femur
|
1.19 percentage change
Standard Deviation 7.77
|
-12.9 percentage change
Standard Deviation 7.67
|
|
Change in Areal Bone Mineral Density at Hip
Femoral neck
|
0.97 percentage change
Standard Deviation 6.12
|
-9.37 percentage change
Standard Deviation 6.39
|
PRIMARY outcome
Timeframe: 4 monthsPercent change in areal bone mineral density (aBMD) assessed by dual energy X-ray absorptiometry (DXA) at 4 months compared to baseline. This will compare aBMD at the distal femur and proximal tibia.
Outcome measures
| Measure |
Zoledronic Acid 5 mg IV Infusion
n=9 Participants
Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
Zoledronic acid: 5 mg zoledronic acid infused intravenously over two hours (2.5mg per hour), given only once, within 21 days of acute traumatic spinal cord injury.
|
Normal Saline 0.9%
n=5 Participants
Infusion of normal saline of equivalent volume to reconstituted zoledronic acid, given only once and run over 2 hours, to occur within 21 days of acute traumatic spinal cord injury.
normal saline 0.9%: Infusion of equivalent volume of 0.9% normal saline to that of the reconstituted zoledronic acid, given only once over two hours, occurring within 21 days of acute traumatic spinal cord injury
|
|---|---|---|
|
Change in Areal Bone Mineral Density at Knee
Distal femur
|
-0.78 percentage change
Standard Deviation 4.46
|
-6.75 percentage change
Standard Deviation 4.04
|
|
Change in Areal Bone Mineral Density at Knee
Proximal tibia
|
-0.24 percentage change
Standard Deviation 11.7
|
-8.56 percentage change
Standard Deviation 14.1
|
PRIMARY outcome
Timeframe: one yearPercent change in areal bone mineral density (aBMD) assessed by dual energy X-ray absorptiometry (DXA) at 12 months post-injury compared to baseline. This will compare aBMD at the hip.
Outcome measures
| Measure |
Zoledronic Acid 5 mg IV Infusion
n=10 Participants
Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
Zoledronic acid: 5 mg zoledronic acid infused intravenously over two hours (2.5mg per hour), given only once, within 21 days of acute traumatic spinal cord injury.
|
Normal Saline 0.9%
n=5 Participants
Infusion of normal saline of equivalent volume to reconstituted zoledronic acid, given only once and run over 2 hours, to occur within 21 days of acute traumatic spinal cord injury.
normal saline 0.9%: Infusion of equivalent volume of 0.9% normal saline to that of the reconstituted zoledronic acid, given only once over two hours, occurring within 21 days of acute traumatic spinal cord injury
|
|---|---|---|
|
Change in Areal Bone Mineral Density at Hip
Total proximal femur
|
-8.2 percentage change
Standard Deviation 3.64
|
-21.3 percentage change
Standard Deviation 8.66
|
|
Change in Areal Bone Mineral Density at Hip
Intertrochanteric femur
|
-8.62 percentage change
Standard Deviation 4.70
|
-19.4 percentage change
Standard Deviation 7.00
|
|
Change in Areal Bone Mineral Density at Hip
Femoral neck
|
-3.93 percentage change
Standard Deviation 5.60
|
-17.0 percentage change
Standard Deviation 11.8
|
PRIMARY outcome
Timeframe: one yearPercent change in areal bone mineral density (aBMD) assessed by dual energy X-ray absorptiometry (DXA) at 12 months post-injury compared to baseline. This will compare aBMD at the distal femur and proximal tibia.
Outcome measures
| Measure |
Zoledronic Acid 5 mg IV Infusion
n=8 Participants
Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
Zoledronic acid: 5 mg zoledronic acid infused intravenously over two hours (2.5mg per hour), given only once, within 21 days of acute traumatic spinal cord injury.
|
Normal Saline 0.9%
n=5 Participants
Infusion of normal saline of equivalent volume to reconstituted zoledronic acid, given only once and run over 2 hours, to occur within 21 days of acute traumatic spinal cord injury.
normal saline 0.9%: Infusion of equivalent volume of 0.9% normal saline to that of the reconstituted zoledronic acid, given only once over two hours, occurring within 21 days of acute traumatic spinal cord injury
|
|---|---|---|
|
Change in Areal Bone Mineral Density at Knee
Distal femur
|
-8.07 percentage change
Standard Deviation 5.2
|
-10.0 percentage change
Standard Deviation 8.7
|
|
Change in Areal Bone Mineral Density at Knee
Proximal tibia
|
-4.54 percentage change
Standard Deviation 9.89
|
-10.0 percentage change
Standard Deviation 18.3
|
SECONDARY outcome
Timeframe: 1 month, 4 months, 12 monthsPopulation: Ons subject in each group did not return for 12-month labs
Change in sCTX from baseline to 1- and 4-months post intervention and 12-months post-injury.
Outcome measures
| Measure |
Zoledronic Acid 5 mg IV Infusion
n=10 Participants
Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
Zoledronic acid: 5 mg zoledronic acid infused intravenously over two hours (2.5mg per hour), given only once, within 21 days of acute traumatic spinal cord injury.
|
Normal Saline 0.9%
n=5 Participants
Infusion of normal saline of equivalent volume to reconstituted zoledronic acid, given only once and run over 2 hours, to occur within 21 days of acute traumatic spinal cord injury.
normal saline 0.9%: Infusion of equivalent volume of 0.9% normal saline to that of the reconstituted zoledronic acid, given only once over two hours, occurring within 21 days of acute traumatic spinal cord injury
|
|---|---|---|
|
Change in Biomarkers of Bone Resorption (sCTX)
1 month
|
-64.1 percentage change
Interval -73.4 to -60.8
|
14.4 percentage change
Interval 11.5 to 15.5
|
|
Change in Biomarkers of Bone Resorption (sCTX)
4 months
|
-45.9 percentage change
Interval -51.4 to -25.6
|
23.9 percentage change
Interval -11.9 to 62.3
|
|
Change in Biomarkers of Bone Resorption (sCTX)
12 months
|
-43.6 percentage change
Interval -57.9 to 33.5
|
-5.11 percentage change
Interval -38.2 to 10.9
|
SECONDARY outcome
Timeframe: 1 month, 4 monthsChange in serum P1NP from baseline to 1- and 4-months post intervention.
Outcome measures
| Measure |
Zoledronic Acid 5 mg IV Infusion
n=10 Participants
Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
Zoledronic acid: 5 mg zoledronic acid infused intravenously over two hours (2.5mg per hour), given only once, within 21 days of acute traumatic spinal cord injury.
|
Normal Saline 0.9%
n=5 Participants
Infusion of normal saline of equivalent volume to reconstituted zoledronic acid, given only once and run over 2 hours, to occur within 21 days of acute traumatic spinal cord injury.
normal saline 0.9%: Infusion of equivalent volume of 0.9% normal saline to that of the reconstituted zoledronic acid, given only once over two hours, occurring within 21 days of acute traumatic spinal cord injury
|
|---|---|---|
|
Change in Biomarkers of Bone Formation (P1NP)
1 month
|
5.66 percentage change
Interval -1.19 to 54.05
|
65.96 percentage change
Interval 48.08 to 101.96
|
|
Change in Biomarkers of Bone Formation (P1NP)
4 months
|
32.43 percentage change
Interval 3.7 to 113.21
|
27.45 percentage change
Interval 18.84 to 213.33
|
SECONDARY outcome
Timeframe: 72-hours and 1 month post intervention.Assessment of the safety and tolerability of zoledronic acid in the acute spinal cord injury population. This will be done by examination reportable adverse events including fevers, flu-like symptoms, GI upset as measures of safety and report of patient's willingness to have participate in physical therapy in the first week after receiving medication as a measure of tolerability
Outcome measures
| Measure |
Zoledronic Acid 5 mg IV Infusion
n=10 Participants
Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
Zoledronic acid: 5 mg zoledronic acid infused intravenously over two hours (2.5mg per hour), given only once, within 21 days of acute traumatic spinal cord injury.
|
Normal Saline 0.9%
n=5 Participants
Infusion of normal saline of equivalent volume to reconstituted zoledronic acid, given only once and run over 2 hours, to occur within 21 days of acute traumatic spinal cord injury.
normal saline 0.9%: Infusion of equivalent volume of 0.9% normal saline to that of the reconstituted zoledronic acid, given only once over two hours, occurring within 21 days of acute traumatic spinal cord injury
|
|---|---|---|
|
Safety and Tolerability of Zoledronic Acid
Fever > 100.9 within 72 hours of study drug infusion
|
7 Participants
|
1 Participants
|
|
Safety and Tolerability of Zoledronic Acid
Flu-like symptoms within 72 hours of study drug infusion
|
6 Participants
|
1 Participants
|
|
Safety and Tolerability of Zoledronic Acid
Acute kidney injury
|
1 Participants
|
1 Participants
|
Adverse Events
Zoledronic Acid 5 mg IV Infusion
Serious events: 2 serious events
Other events: 7 other events
Deaths: 0 deaths
Normal Saline 0.9%
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Zoledronic Acid 5 mg IV Infusion
n=10 participants at risk
Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
Zoledronic acid: 5 mg zoledronic acid infused intravenously over two hours (2.5mg per hour), given only once, within 21 days of acute traumatic spinal cord injury.
|
Normal Saline 0.9%
n=5 participants at risk
Infusion of normal saline of equivalent volume to reconstituted zoledronic acid, given only once and run over 2 hours, to occur within 21 days of acute traumatic spinal cord injury.
normal saline 0.9%: Infusion of equivalent volume of 0.9% normal saline to that of the reconstituted zoledronic acid, given only once over two hours, occurring within 21 days of acute traumatic spinal cord injury
|
|---|---|---|
|
Renal and urinary disorders
Acute kidney injury
|
10.0%
1/10 • Number of events 1 • 1 month
Subject #7 developed chest pain within 24-hours of study drug administration. Cardiac workup was negative but laboratory studies found elevated creatine phosphokinase (CPK). Baseline and periodic serum CPK studies over the first 7 days after study drug administration were added to the protocol for subsequent patients.
|
20.0%
1/5 • Number of events 1 • 1 month
Subject #7 developed chest pain within 24-hours of study drug administration. Cardiac workup was negative but laboratory studies found elevated creatine phosphokinase (CPK). Baseline and periodic serum CPK studies over the first 7 days after study drug administration were added to the protocol for subsequent patients.
|
|
Musculoskeletal and connective tissue disorders
Non-cardiac chest pain
|
10.0%
1/10 • Number of events 1 • 1 month
Subject #7 developed chest pain within 24-hours of study drug administration. Cardiac workup was negative but laboratory studies found elevated creatine phosphokinase (CPK). Baseline and periodic serum CPK studies over the first 7 days after study drug administration were added to the protocol for subsequent patients.
|
0.00%
0/5 • 1 month
Subject #7 developed chest pain within 24-hours of study drug administration. Cardiac workup was negative but laboratory studies found elevated creatine phosphokinase (CPK). Baseline and periodic serum CPK studies over the first 7 days after study drug administration were added to the protocol for subsequent patients.
|
Other adverse events
| Measure |
Zoledronic Acid 5 mg IV Infusion
n=10 participants at risk
Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
Zoledronic acid: 5 mg zoledronic acid infused intravenously over two hours (2.5mg per hour), given only once, within 21 days of acute traumatic spinal cord injury.
|
Normal Saline 0.9%
n=5 participants at risk
Infusion of normal saline of equivalent volume to reconstituted zoledronic acid, given only once and run over 2 hours, to occur within 21 days of acute traumatic spinal cord injury.
normal saline 0.9%: Infusion of equivalent volume of 0.9% normal saline to that of the reconstituted zoledronic acid, given only once over two hours, occurring within 21 days of acute traumatic spinal cord injury
|
|---|---|---|
|
General disorders
Fever
|
70.0%
7/10 • Number of events 7 • 1 month
Subject #7 developed chest pain within 24-hours of study drug administration. Cardiac workup was negative but laboratory studies found elevated creatine phosphokinase (CPK). Baseline and periodic serum CPK studies over the first 7 days after study drug administration were added to the protocol for subsequent patients.
|
20.0%
1/5 • Number of events 1 • 1 month
Subject #7 developed chest pain within 24-hours of study drug administration. Cardiac workup was negative but laboratory studies found elevated creatine phosphokinase (CPK). Baseline and periodic serum CPK studies over the first 7 days after study drug administration were added to the protocol for subsequent patients.
|
|
General disorders
Flu-like symptoms
|
60.0%
6/10 • Number of events 6 • 1 month
Subject #7 developed chest pain within 24-hours of study drug administration. Cardiac workup was negative but laboratory studies found elevated creatine phosphokinase (CPK). Baseline and periodic serum CPK studies over the first 7 days after study drug administration were added to the protocol for subsequent patients.
|
20.0%
1/5 • Number of events 1 • 1 month
Subject #7 developed chest pain within 24-hours of study drug administration. Cardiac workup was negative but laboratory studies found elevated creatine phosphokinase (CPK). Baseline and periodic serum CPK studies over the first 7 days after study drug administration were added to the protocol for subsequent patients.
|
|
Musculoskeletal and connective tissue disorders
elevated creatine phosphokinase (CPK)
|
16.7%
1/6 • Number of events 1 • 1 month
Subject #7 developed chest pain within 24-hours of study drug administration. Cardiac workup was negative but laboratory studies found elevated creatine phosphokinase (CPK). Baseline and periodic serum CPK studies over the first 7 days after study drug administration were added to the protocol for subsequent patients.
|
0.00%
0/3 • 1 month
Subject #7 developed chest pain within 24-hours of study drug administration. Cardiac workup was negative but laboratory studies found elevated creatine phosphokinase (CPK). Baseline and periodic serum CPK studies over the first 7 days after study drug administration were added to the protocol for subsequent patients.
|
Additional Information
Christina V Oleson, MD
MetroHealth Rehabilitation Institute
Phone: 216-778-4414
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place