OsteoporosisPhase 4NCT02489825
Study About the Effect of Preventive Adjacent Level Cement Augmentation After Osteoporotic Vertebral Compression Fractures
A Phase 4 study testing Augmentation vertebroplasty and Augmentation and prophylactic vertebroplasty in people with Osteoporosis and Vertebral Fracture, run by University of Bern at 1 site in Switzerland.
Trial summary
Vertebroplasty itself is challenged regarding its clinical efficacy. While two randomized controlled trials (RCTs) with substantial methodological problems have led to an intense discussion another RCT with larger case numbers, more representative inclusion criteria and a more consistent and sound methodology has… Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Osteoporosis, Vertebral Fracture
- What is being tested?
- Augmentation vertebroplasty and Augmentation and prophylactic vertebroplasty
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jan 2015to Feb 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 55 years
- Written informed consent
- Single level acute (< 6 weeks) vertebral compression fracture
- Fracture due to diagnosed or presumed underlying primary or secondary osteoporosis
- Patients with Association for the study of Osteosynthesis (AO) type A1.x fractures and A3.1 fractures may be included in the study
- Target Vertebral Compression Fracture (VCF) is between T10 and L4
Show all 16Show fewer
- Target VCF to be treated shows either: height change - an acute (< 6 weeks) change in VB height (>15% height loss) with height loss at the anterior or middle portion of the VB consistent with a worsening of 1 or more grades acc to Genant
- OR positive MRI or bone scan - VB shows hyperintense signal on MRI-T2 or STIR sequence
- OR target VB is positive on radionuclide bone scan
- Back pain correlating with the location of the VCF
- Treatment of target and adjacent VCFs is technically feasible by and clinically appropriate for vertebroplasty
- No previous VCFs
- No major surgery of the spine planned for at least 6 months following enrollment
- Pre-treatment back pain by numerical rating scale (NRS) score > 4 (0-10 scale)
- Subject is able to understand the risks and benefits of participating in the study and is willing to provide written informed consent
- Psychosocially, mentally and physically able to fully comply with the protocol requirements for the duration of the study including adhering to scheduled visits, treatment plan, completing forms and other study procedures.
Who cannot join
- VB morphology or configuration is such that vertebroplasty is not technically feasible for the targeted and adjacent VCFs
- Fracture due to high-energy trauma
- Suspected OR proven cancer inside index vertebral body
- Disabling back pain due to causes other than acute fracture (e.g., sacroiliac fracture, symptomatic degenerative disc disease, lumbar spinal stenosis)
- Any painful VCF with fracture age > 6 weeks
- Patients with primary tumors of the bone (e.g., osteosarcoma) or solitary plasmacytoma at site of the index or adjacent VCF
Show all 17Show fewer
- Any objective evidence of neurologic compromise at baseline.
- Previous balloon kyphoplasty, VBS or vertebroplasty for any VCF
- Significant clinical comorbidity that may potentially interfere with follow-up (e.g., dementia, severe comorbid illness)
- Patients requiring the use of high-dose steroid (>= 100mg prednisone or 20 mg dexamethasone per day), IV pain medication, or nerve block to control chronic back pain unrelated to index VCF
- Spinal cord compression or canal compromise requiring decompression
- Patients with osteoblastic tumors at the site of the index VCF
- MRI contraindication (e.g. cerebral aneurysm clips, pacemaker, implanted biostimulators, cochlear implants, penile prosthesis)
- Spinal instability as indicated by neurologic deficit, kyphosis >30°, compression >50%, translation >4 mm, interspinous-process widening.
- Pre-existing conditions contrary to vertebroplasty, such as: irreversible coagulopathy or bleeding disorder
- Allergy to bone cement.
- Any evidence of VB or systemic infection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pilot Study: Does Preventive Adjacent Level Cement Augmentation Positively Affect Reoperation Rates After Osteoporotic Vertebral Compression Fractures?
Vertebroplasty itself is challenged regarding its clinical efficacy. While two randomized controlled trials (RCTs) with substantial methodological problems have led to an intense discussion another RCT with larger case numbers, more representative inclusion criteria and a more consistent and sound methodology has revealed results that mirror the investigators' own clinical experience. In their daily practice, the investigators have further advanced their treatment concept and routinely apply prophylactic augmentations with VP using an algorithm. Biomechanical studies support their approach, but clinical studies are rare so far. Prophylactic augmentation with balloon kyphoplasty has not shown convincing effects in a small pilot study. Given the above mentioned methodological and clinical disputes and the call for high-evidence studies about VP, the investigators aim at generating a reliable sample size calculation and preliminary results for a future multicenter RCT about prophylactic adjacent level augmentation with VP in single level osteoporotic compression fractures.
Read the detailed description
Background
Despite current academic debates percutaneous vertebroplasty (VP) has been convincingly used for the treatment of osteoporotic compression fractures all around the world. Polymethylmethacrylate bone cement is directly injected into a fractured vertebral body through one or two bone biopsy needles to stabilize the fracture fragments and to possibly improve the vertebral body height. The fracture pain represents a significant burden for the patients, limiting physical function, quality of life and increasing social isolation.
The immediate and clinically relevant pain alleviation after vertebroplasty does therefore have a large impact on patients' mobility, autonomy and quality of life.
The current state of the art in the treatment of acute osteoporotic vertebral compression fractures that are nonresponsive to conservative treatment is still augmentation of the fractures with VP or balloon kyphoplasty (BKP) given an intact posterior vertebral body wall. BKP is claimed to be saver by reducing the occurrence of cement leakages and more effective in reducing the fracture, i.e. reconstituting vertebral body height. While the first argument largely depends on the definition of an adverse event, i.e. is an asymptomatic radiologically visible cement leakage truly a complication, the second argument could not hold its promise since the regained vertebral body height is partially lost after balloon deflation. This problem is tackled by further developed BKP technologies like vertebral body stenting (VBS). From a cost-effectiveness perspective, VP is superior to conservative medical care and one can postulate that it is hence also more cost-effective than BKP which is a much more costly treatment option.In addition, it is the only prophylactic augmentation option that does not "destroy" intact unfractured bone structures by deployment of the balloon but does only augment them. It is hence the least aggressive augmentation option for prophylaxis.
Osteoporosis as the underlying disease leads to an increased risk of fractures of the adjacent vertebral bodies, with incidences up to 22% in the first year. After fracture augmentation new fractures in the spine can occur. This leads to reoperations in a frail population with high numbers of American Society of Anaesthesiologists (ASA) 3-4 patients. Any non-life-saving surgical intervention in these patients needs to be avoided. Therefore, prophylactic augmentation of the adjacent non-fractured vertebral bodies is a treatment option which is safe and may reduce reoperation rates. Since VP is currently under scientific and clinical scrutiny and calls for level-one-evidence become audible everywhere, the investigators plan to assess the hypothesis that prophylactic augmentation significantly decreases reoperation rates for adjacent new fractures with a randomized controlled trial.
Objective
The aim of the proposed study is to show the effect of preventive augmentations of adjacent vertebral bodies on 6 (12) months reoperation rates.
Subjects with an acute (<= 6 weeks) single level osteoporotic compression fracture, meeting the inclusion criteria and having no exclusion criterion will be randomized to either single level fracture fixation with vertebroplasty or triple level augmentation with VP fixation of the fracture and additional prophylactic vertebroplasty in both adjacent levels. The hypothesis is that prophylactic VP augmentation of both adjacent vertebral bodies in acute single level osteoporotic compression fractures results in significantly lower reoperation rates for new spinal fractures within 6 months after surgery compared to isolated single level fracture fixation.
Methods
This is an open label mono-center randomized controlled pilot trial. Given the timeframe and budget of the study, the investigators aim at conducting a pilot trial for clinically verifying the sample size calculation in order to have a sound basis of information for planning a larger multicenter trial. The inclusion of primary cases will last for 12 months, the followup intervals for each case will be 2 and 6 months since the large majority of new fractures appears within that time window. 12 months followup will be conducted by mail/telephone interview. Preliminary calculation of results, i.e. a new corrected sample size will hence be carried out at the end of one and a half years. Two treatment groups will be compared:
Group 1: single level fracture fixation with vertebroplasty, Group 2: triple level augmentation with VP fixation of the fracture and additional prophylactic vertebroplasty in both the adjacent levels.
- Conditions
- Osteoporosis, Vertebral Fracture
- Being tested
- Augmentation vertebroplasty, Augmentation and prophylactic vertebroplasty
- Keywords
- randomized controlled trial, vertebral fracture, osteoporosis, vertebroplasty, augmentation
- Medical subject headings
- Osteoporosis, Spinal Fractures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Augmentation vertebroplastyProcedure or surgery
Cement augmentation of fractured vertebral body
Augmentation and prophylactic vertebroplastyProcedure or surgery
Cement augmentation of fractured vertebral body and prophylactic augmentation of both adjacent vertebral bodies
| Study group | Role | What they receive |
|---|---|---|
| Augmentation vertebroplasty | Other | Single level fracture fixation with vertebroplasty Receives: Procedure: Augmentation vertebroplasty |
| Augmentation and prophylactic vertebroplasty | Other | Triple level augmentation with VP fixation of the fracture and additional prophylactic vertebroplasty in both the adjacent levels Receives: Procedure: Augmentation and prophylactic vertebroplasty |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of new operations within 6 months after vertebroplasty due to adjacent or distant segment fracture.
Measured by interview, clinical \& radiographic assessment
Measured: 6 months after index surgery
Secondary outcomes (2)
Disease specific quality of life (COMI back form)
Measured by questionnaire
Measured: 6 months after index surgery
General quality of life
Measured by questionnaire
Measured: 6 months after index surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2015 (estimated)
- Study startJan 2015
- Primary completionFeb 2022
- Study completionFeb 2022
Why it stopped: Death of study initiator
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Bern
- Sponsor type
- University, hospital or other
- Collaborators
- Sonnenhof Hospital, Bern
- Responsible party
- Sponsor
- Investigators
- Paul Heini, MD, professor, head of dept., Principal investigator, Sonnenhof Hospital, Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02489825
- Sponsor's protocol ID
- 008/13
- Other IDs
- 13-01-F
- Status last verified
- Mar 2023
- First submitted
- 25 Jun 2015
- Last updated
- 16 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Diel P, Freiburghaus L, Roder C, Benneker LM, Popp A, Perler G, Heini PF. Safety, effectiveness and predictors for early reoperation in therapeutic and prophylactic vertebroplasty: short-term results of a prospective case series of patients with osteoporotic vertebral fractures. Eur Spine J. 2012 Aug;21 Suppl 6(Suppl 6):S792-9. doi: 10.1007/s00586-011-1989-x. Epub 2011 Aug 30.
PubMed 21877131
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study: Does Preventive Adjacent Level Cement Augmentation Positively Affect Reoperation Rates After Osteoporotic Vertebral Compression Fractures?
- ClinicalTrials.gov ID
- NCT02489825
- Acronym / sponsor ID
- 008/13
- Conditions
- Osteoporosis, Vertebral Fracture
- Keywords
- randomized controlled trial, vertebral fracture, osteoporosis, vertebroplasty, augmentation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Death of study initiator
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of BernUniversity, hospital or other
- Collaborators
- Sonnenhof Hospital, Bern
- Study start
- Jan 2015
- Primary completion
- Feb 2022 (actual)
- Study completion
- Feb 2022 (actual)
- First posted
- 3 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Vertebroplasty itself is challenged regarding its clinical efficacy. While two randomized controlled trials (RCTs) with substantial methodological problems have led to an intense discussion another RCT with larger case numbers, more representative inclusion criteria and a more consistent and sound methodology has revealed results that mirror the investigators' own clinical experience. In their daily practice, the investigators have further advanced their treatment concept and routinely apply prophylactic augmentations with VP using an algorithm. Biomechanical studies support their approach, but clinical studies are rare so far. Prophylactic augmentation with balloon kyphoplasty has not shown convincing effects in a small pilot study. Given the above mentioned methodological and clinical disputes and the call for high-evidence studies about VP, the investigators aim at generating a reliable sample size calculation and preliminary results for a future multicenter RCT about prophylactic adjacent level augmentation with VP in single level osteoporotic compression fractures.
Detailed description
Background
Despite current academic debates percutaneous vertebroplasty (VP) has been convincingly used for the treatment of osteoporotic compression fractures all around the world. Polymethylmethacrylate bone cement is directly injected into a fractured vertebral body through one or two bone biopsy needles to stabilize the fracture fragments and to possibly improve the vertebral body height. The fracture pain represents a significant burden for the patients, limiting physical function, quality of life and increasing social isolation.
The immediate and clinically relevant pain alleviation after vertebroplasty does therefore have a large impact on patients' mobility, autonomy and quality of life.
The current state of the art in the treatment of acute osteoporotic vertebral compression fractures that are nonresponsive to conservative treatment is still augmentation of the fractures with VP or balloon kyphoplasty (BKP) given an intact posterior vertebral body wall. BKP is claimed to be saver by reducing the occurrence of cement leakages and more effective in reducing the fracture, i.e. reconstituting vertebral body height. While the first argument largely depends on the definition of an adverse event, i.e. is an asymptomatic radiologically visible cement leakage truly a complication, the second argument could not hold its promise since the regained vertebral body height is partially lost after balloon deflation. This problem is tackled by further developed BKP technologies like vertebral body stenting (VBS). From a cost-effectiveness perspective, VP is superior to conservative medical care and one can postulate that it is hence also more cost-effective than BKP which is a much more costly treatment option.In addition, it is the only prophylactic augmentation option that does not "destroy" intact unfractured bone structures by deployment of the balloon but does only augment them. It is hence the least aggressive augmentation option for prophylaxis.
Osteoporosis as the underlying disease leads to an increased risk of fractures of the adjacent vertebral bodies, with incidences up to 22% in the first year. After fracture augmentation new fractures in the spine can occur. This leads to reoperations in a frail population with high numbers of American Society of Anaesthesiologists (ASA) 3-4 patients. Any non-life-saving surgical intervention in these patients needs to be avoided. Therefore, prophylactic augmentation of the adjacent non-fractured vertebral bodies is a treatment option which is safe and may reduce reoperation rates. Since VP is currently under scientific and clinical scrutiny and calls for level-one-evidence become audible everywhere, the investigators plan to assess the hypothesis that prophylactic augmentation significantly decreases reoperation rates for adjacent new fractures with a randomized controlled trial.
Objective
The aim of the proposed study is to show the effect of preventive augmentations of adjacent vertebral bodies on 6 (12) months reoperation rates.
Subjects with an acute (<= 6 weeks) single level osteoporotic compression fracture, meeting the inclusion criteria and having no exclusion criterion will be randomized to either single level fracture fixation with vertebroplasty or triple level augmentation with VP fixation of the fracture and additional prophylactic vertebroplasty in both adjacent levels. The hypothesis is that prophylactic VP augmentation of both adjacent vertebral bodies in acute single level osteoporotic compression fractures results in significantly lower reoperation rates for new spinal fractures within 6 months after surgery compared to isolated single level fracture fixation.
Methods
This is an open label mono-center randomized controlled pilot trial. Given the timeframe and budget of the study, the investigators aim at conducting a pilot trial for clinically verifying the sample size calculation in order to have a sound basis of information for planning a larger multicenter trial. The inclusion of primary cases will last for 12 months, the followup intervals for each case will be 2 and 6 months since the large majority of new fractures appears within that time window. 12 months followup will be conducted by mail/telephone interview. Preliminary calculation of results, i.e. a new corrected sample size will hence be carried out at the end of one and a half years. Two treatment groups will be compared:
Group 1: single level fracture fixation with vertebroplasty, Group 2: triple level augmentation with VP fixation of the fracture and additional prophylactic vertebroplasty in both the adjacent levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Augmentation vertebroplasty | Other | Procedure: Augmentation vertebroplastySingle level fracture fixation with vertebroplasty |
| Augmentation and prophylactic vertebroplasty | Other | Procedure: Augmentation and prophylactic vertebroplastyTriple level augmentation with VP fixation of the fracture and additional prophylactic vertebroplasty in both the adjacent levels |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Age ≥ 55 years
- Written informed consent
- Single level acute (< 6 weeks) vertebral compression fracture
- Fracture due to diagnosed or presumed underlying primary or secondary osteoporosis
- Patients with Association for the study of Osteosynthesis (AO) type A1.x fractures and A3.1 fractures may be included in the study
Key exclusion criteria (17 listed)
- VB morphology or configuration is such that vertebroplasty is not technically feasible for the targeted and adjacent VCFs
- Fracture due to high-energy trauma
- Suspected OR proven cancer inside index vertebral body
- Disabling back pain due to causes other than acute fracture (e.g., sacroiliac fracture, symptomatic degenerative disc disease, lumbar spinal stenosis)
- Any painful VCF with fracture age > 6 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Augmentation vertebroplastyCement augmentation of fractured vertebral body | Procedure or surgery | Augmentation vertebroplasty |
| Augmentation and prophylactic vertebroplastyCement augmentation of fractured vertebral body and prophylactic augmentation of both adjacent vertebral bodies | Procedure or surgery | Augmentation and prophylactic vertebroplasty |
Primary outcome
Number of new operations within 6 months after vertebroplasty due to adjacent or distant segment fracture.
Time frame: 6 months after index surgery
Measured by interview, clinical \& radiographic assessment
2 secondary outcomes
Disease specific quality of life (COMI back form)
Time frame: 6 months after index surgery
General quality of life
Time frame: 6 months after index surgery
Results and safety
The study was stopped early (reason given: Death of study initiator). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2023.
- Results publication: PubMed 21877131Diel P, Freiburghaus L, Roder C, Benneker LM, Popp A, Perler G, Heini PF. Safety, effectiveness and predictors for early reoperation in therapeutic and prophylactic vertebroplasty: short-term results of a prospective case series of patients with osteoporotic vertebral fractures. Eur Spine J. 2012 Aug;21 Suppl 6(Suppl 6):S792-9. doi: 10.1007/s00586-011-1989-x. Epub 2011 Aug 30.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Heini, MD, professor, head of dept. principal investigator
Sonnenhof Hospital, Bern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Augmentation vertebroplasty and Augmentation and prophylactic vertebroplasty in people with Osteoporosis and Vertebral Fracture, run by University of Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Death of study initiator). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of new operations within 6 months after vertebroplasty due to adjacent or distant segment fracture. (time frame: 6 months after index surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02489825, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2023.