Investigational Vertebroplasty Efficacy and Safety Trial (INVEST)

This is unpublished

Investigational Vertebroplasty Efficacy and Safety Trial (INVEST)

In vertebroplasty, a needle is inserted through the skin into the fractured bone. A bone cement is injected. The cement hardens, stabilizes the bone and prevents further collapse. This stops the pain caused by bone rubbing against bone.

Vertebroplasty is a new treatment for painful spinal compression fractures that are caused by osteoporosis. Spontaneous compression fractures are a significant public health concern since these fractures occur in more than 700,000 Americans annually. The pain associated with these fractures may be excruciating, and treatment options, before the advent of vertebroplasty, were limited. Pain medications, bed rest, bracing and major back surgery have previously represented the main treatment choices.

The primary objective of this research project is to examine the clinical efficacy of percutaneous vertebroplasty for patients suffering from vertebral compression fractures (VCFs) caused by osteoporosis. This sham-controlled research will measure both the treatment effect of the procedure (in terms of pain relief and multiple functional status indicators) and its cost effectiveness. The MCRC serves as the data coordinating and statistical analysis center for the trial. Subjects will be equally randomized to receive either the vertebroplasty or the control intervention. The control includes the insertion of a needle into the vertebra to simulate what the actual procedure entails. Patients will complete both clinical and resource utilization questionnaires at baseline and periodic intervals over a two year follow up period.

Most fractures occur in the: Middle, or thoracic spine. Consists of 12 vertebrae, each carrying a set of ribs, or in the: Lower or lumbar spine, consists of the five largest and strongest vertebrae.

Principal Investigator

Data Coordinating Site PI	UW Clinical Site PI
Jerry Jarvik, MD, MPH Professor, Radiology and Neurosurgery Section Chief – Neuroradiology Adjunct Professor, Health Services	Basavaraj Ghodke, MD Acting Assistant Professor, Radiology Harborview Medical Center

Research Questions

1. To test the hypothesis that percutaneous vertebroplasty improves functional status and health related quality of life, we will perform a prospective, randomized-controlled, blinded trial comparing percutaneous vertebroplasty to sham vertebroplasty. We will employ sensitive, disease-specific and general health related quality of life outcome measures to compare patients treated with percutaneous vertebroplasty with patients treated by sham vertebroplasty.

2. To test the hypothesis that short- and long-term pain relief achieved with percutaneous vertebroplasty is greater than that from a placebo, we will employ pain-related outcomes measures in the trial proposed in Aim 1.

3. To determine the incremental cost-effectiveness of vertebroplasty versus sham vertebroplasty, we will employ resource utilization measurements in the trial proposed in Aim 1 to perform a cost-effectiveness analysis of vertebroplasty compared to sham vertebroplasty.

Successful implementation of the trial and of the studies described above will provide compelling evidence regarding the true efficacy of percutaneous vertebroplasty to allow rational, cost-effective decision-making in caring for patients suffering from painful, osteoporotic compression fractures.

Research Highlights

1. CEMENTING THE EVIDENCE: TIME FOR A RANDOMIZED TRIAL OF VERTEBROPLASTY

Jeffrey G. Jarvik MD, MPH
Richard A. Deyo, MD, MPH

Objective:

Percutaneous vertebroplasty is a technique for treating low back pain that appears to be rapidly disseminating throughout the United States. Yet, there are still no randomized, controlled trials that compare the long-term outcomes of percutaneous vertebroplasty to a control therapy.

Conclusions:

Vertebroplasty may well be an effective and even cost-effective method for treating low back pain. If the technique is as good as its promoters suggest, then it should be straightforward to demonstrate its efficacy in a well-designed, controlled trial. The time is right to demonstrate the technique’s advantages and convince the scientific community, as well as the public, of its worth.

2. PERADOXICAL CEREBRAL ARTERIAL EMBOLIZATION OF CEMENT DURING INTRAOPERATIVE VERTEBROPLASTY: CASE REPORT

Rebecca Scroop
Joseph Eskridge
Gavin W. Britz

Objective:

Paradoxical cerebral embolism of cement occurred in a 78-year-old woman after cement-assisted transpedicular spinal fixation surgery. Multiple pulmonary emboli of polymethylmethacrylate precipitated pulmonary hypertension and right-to-left shunting into the systemic circulation through a patent foramen ovale. This rare complication occurred because of failure to recognize venous migration of cement during the procedure and the injection of multiple levels in one setting. Although this was an open procedure, the technical aspects were the same as for vertebroplasty and the precautions should be applied to percutaneous vertebroplasty.

Research Methods

The trial is designed to be a blinded, randomized investigation. The subjects will be randomized to either the control intervention group or the investigational intervention (vertebroplasty treatment) group. The subjects will be blinded to their intervention and the research staff completing the post-procedural follow-up questionnaires will also be blind to treatment assignment. Patient data will be analyzed for the safety and efficacy of the vertebroplasty procedure as well as its incremental cost effectiveness.

Study participants will be recruited from patients who are scheduled for vertebroplasty evaluations in multiple US and international clinical sites. The current US sites are the Mayo Clinic (MN), Mission Health (NC), University of Washington (UWA), Oregon Health Sciences University (OHSU), University of California at Los Angeles (UCLA), and the University of Virginia (UVA). International sites in Australia, England and Canada are also participating.

The research team will first ask potential subjects to sign a research release form to determine eligibility. The investigator and the research coordinator will describe the study to eligible patients and informed consent will be obtained prior to conducting baseline evaluations and randomization.

Conclusion:

Assuming that venous extravasation and pulmonary emboli can and probably do occur to some degree in association with clinically uncomplicated vertebroplasty, it is prudent to limit the levels treated at a single setting. In this case, a total of 15 levels were treated with transpedicular PMMA and resulted in significantly raised pulmonary pressures. Although not based on experimental or hard clinical evidence, we recommend that in patients without underlying pulmonary disease, a maximum of three levels be treated in a single setting, even with good fluoroscopic monitoring. Unlike this case, vertebroplasty does not require general anesthesia, and it is our practice to use local anesthesia and neurolept sedation that allows early detection of any changes in the clinical condition of the patient.

Eligibility criteria are as follows:

Patient is > 50 years of age.
Patient is being seen as an outpatient.
Patient has pain from one or more compression fractures of the vertebrae in the areas T4 to L5 confirmed with a physical exam, and a plain film X-ray.
Patient’s fracture occurred in the previous 12 months.
Patient has normal (or correctable) coagulation.
Patient has normal renal function or venography is not anticipated.
Patient has no contraindications for conscious sedation.
Patient reports pain from the compression fracture(s) of at least three (3) on a numerical pain scale.
Patient has access to a telephone.
Patient is not pregnant
Patient speaks English well enough to answer all health questions.
Patient has a confirmed diagnosis of osteoporosis by a referring physician and/or medical history and physical exam OR osteopenia on plain film.
Patient has no cord compression either on physical exam or imaging.
Patient has no mental incapacity or dementia that makes him/her unable to give informed consent.
Patient has tried medical therapy for pain from the compression fracture(s).
Patient has no pedicle fractures.
Patient has no active local or systemic infection.
Patient has not had surgery (within the last 60 days).
Patient has no concomitant hip fracture.
Patient has no malignant tumor deposit (multiple myeloma), tumor mass, or tumor extension into the epidural space at the level of the fracture to be treated confirmed with a CT scan.