Clinical Trial Results:
Efficacy of zoledronic acid 5 mg for chronic low back pain due to Modic changes
|
Summary
|
|
EudraCT number |
2008-005351-14 |
Trial protocol |
FI |
Global end of trial date |
19 Mar 2012
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
04 Oct 2019
|
First version publication date |
04 Oct 2019
|
Other versions |
|
Summary report(s) |
Efficacy of zoledronic acid for chronic low back pain associated with Modic changes in magnetic resonance imaging The Effect of zoledronic acid on type and volume of Modic changes among patients with low back pain |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
CZOL446HFI03
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01330238 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
University of Oulu, Department of Physical and Rehabilitation Medicine
|
||
Sponsor organisation address |
PL 5000, Oulu, Finland, 90014
|
||
Public contact |
Department of Physical and Rehabilitation Medicine, Department of Physical and Rehabilitation Medicine, 041 4462859, jaro.karppinen@ttl.fi
|
||
Scientific contact |
Department of Physical and Rehabilitation Medicine, Department of Physical and Rehabilitation Medicine, 041 4462859, jaro.karppinen@ttl.fi
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
19 Mar 2012
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
19 Mar 2012
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
19 Mar 2012
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Bisphosphonates could be effective in Modic changes causing low back pain through two mechanisms: 1.) they could consolidate the vertebral bodies thereby improving the tolerance to mechanical load and 2.) they could disminish inflammation as observed recently in case of ibandronate in an experimental inflammation model
|
||
Protection of trial subjects |
Before administration of the infusion, all patients re- ceived oral ibuprofen 600 mg or paracetamol 1 g as prophylaxis for potential acute phase reactions such as flu-like symptoms, headache or fever. Patients were advised to use the same medication should post-dose symptoms appear. They all also received 100 000 units of Vitamin D (Vigantol®) orally to prevent hypocalcae- mia. Information on use of the concomitant medication and hospital admissions were recorded. Blood samples were taken for the assessment of safety, inflammatory mediators and markers of bone turnover at baseline, one month and one year.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Nov 2008
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety, Efficacy, Ethical reason, Regulatory reason, Scientific research | ||
Long term follow-up duration |
1 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Finland: 40
|
||
Worldwide total number of subjects |
40
|
||
EEA total number of subjects |
40
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
40
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
||||||||||
|
Recruitment
|
||||||||||
Recruitment details |
Patients referred from primary health care units to Oulu University Hospital, where they were screened, between 11/2008 and 3/2011.Blood samples for the assessment of safety, inflammatory mediators and markers of bone turnover at bl, 1 m and 1 y.Clinical examination, MRI of lumbar spine, a signed informed, visual analog scale, Oswestry, RAND-36. | |||||||||
|
Pre-assignment
|
||||||||||
Screening details |
Inclusion criteria were low back symptoms for at least three months, an LBP intensity of at least six (6) on a 10-cm Visual Analog Scale (VAS) or an Oswestry Disability Index (ODI) of at least 30% [21], and an M1, mixed M1/2 or M2 in MRI performed within six months at most prior to enrolment. | |||||||||
|
Period 1
|
||||||||||
Period 1 title |
Overall trial (overall period)
|
|||||||||
Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
|
|||||||||
Blinding used |
Double blind | |||||||||
Roles blinded |
Investigator, Monitor, Subject, Data analyst, Carer | |||||||||
Blinding implementation details |
A master randomization list was generated by a computer in blocks of eight, containing four placebo and four ZA allocations in random order. Patients were assigned a unique randomization number according to the order of inclusion. Patients, the principal investiga- tor performing the screening and follow-up assessments, the nurse, the radiologist evaluating the MRI scans, and the statistician were blinded to the treatment allocation. The ZA and placebo were supplied in in identical bottles.
|
|||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||
|
Arm title
|
Zoledronic acid | |||||||||
Arm description |
Patients were randomized to receive a single intravenous infusion of 5 mg ZA in 100 ml saline (n=20) or 100 ml saline as placebo (n = 20) over a 15-minute period. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Aclasta/zoledronic acid 5 mg
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Infusion
|
|||||||||
Routes of administration |
Intravenous use
|
|||||||||
Dosage and administration details |
patients were randomized to receive a single intravenous infusion of 5 mg ZA in 100 ml saline (n=20) or 100 ml saline as placebo (n = 20) over a 15-minute period.
|
|||||||||
|
Arm title
|
Placebo | |||||||||
Arm description |
Patients were randomized to receive a single intravenous infusion of 5 mg ZA in 100 ml saline (n=20) or 100 ml saline as placebo (n = 20) over a 15-minute period. | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
100 ml saline as placebo
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Infusion
|
|||||||||
Routes of administration |
Intravenous use
|
|||||||||
Dosage and administration details |
Patients were randomized to receive a single intravenous infusion of 5 mg ZA in 100 ml saline (n=20) or 100 ml saline as placebo (n = 20) over a 15-minute period.
|
|||||||||
|
||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Zoledronic acid
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patients were randomized to receive a single intravenous infusion of 5 mg ZA in 100 ml saline (n=20) or 100 ml saline as placebo (n = 20) over a 15-minute period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Patients were randomized to receive a single intravenous infusion of 5 mg ZA in 100 ml saline (n=20) or 100 ml saline as placebo (n = 20) over a 15-minute period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Zoledronic acid
|
||
Reporting group description |
Patients were randomized to receive a single intravenous infusion of 5 mg ZA in 100 ml saline (n=20) or 100 ml saline as placebo (n = 20) over a 15-minute period. | ||
Reporting group title |
Placebo
|
||
Reporting group description |
Patients were randomized to receive a single intravenous infusion of 5 mg ZA in 100 ml saline (n=20) or 100 ml saline as placebo (n = 20) over a 15-minute period. | ||
Subject analysis set title |
Treatment effect by comparing the change in the outcomes
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
independent samples t-test
|
||
|
|||||||||||||
End point title |
Change in intensity of low back pain | ||||||||||||
End point description |
Primary endpoint was change in intensity of low back pain (10 cm VAS) form baseline to one year
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
The mean difference (MD) between the treatment groups in the primary outcome, intensity of LBP
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment effect by comparing change in outcome | ||||||||||||
Statistical analysis description |
independent samples t-test
|
||||||||||||
Comparison groups |
Zoledronic acid v Placebo
|
||||||||||||
Number of subjects included in analysis |
40
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
|||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
|||||||||||||
|
|||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events were asked at 1 month and 1 year follow-up.The occurrence of any adverse effects was observed during the infusion and inquired about at each of the follow-up visits.
|
||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Despite prophylaxis, acute post-infusion phase reactions (fever, headache, myalgia, arthralgia, pain, nau- sea and flu-like symptoms) were observed in 19/20 patients in the ZA vs. 7/20 patients in the placebo group
|
||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||
Dictionary version |
22.0
|
||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||
Reporting group title |
Zoledronic acid group
|
||||||||||||||||||||||||||||||
Reporting group description |
Patients received a single intravenous infusion of 5 mg ZA in 100 ml saline. Despite prophylaxis, acute post-infusion phase reactions (fever, headache, myalgia, arthralgia, pain, nau- sea and flu-like symptoms) were observed in 19/20 patients in the ZA vs. 7/20 patients in the placebo group. One event met the criteria for serious adverse effect (SAE) in the ZA group; sinusitis requiring temporary hospitalization after the infusion. | ||||||||||||||||||||||||||||||
Reporting group title |
Placebo group
|
||||||||||||||||||||||||||||||
Reporting group description |
Patients received a single intravenous infusion of 100 ml saline as placebo | ||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
|||
| http://www.ncbi.nlm.nih.gov/pubmed/24588905 |
|||
