Vertebroplasty for the Treatment of Fractures Due to Osteoporosis

Investigational Vertebroplasty Efficacy and Safety Trial (INVEST)

Vertebroplasty is a procedure used to stabilize broken vertebrae, the bones that form the spine. This study will evaluate the effectiveness of vertebroplasty for the treatment of fractures due to osteoporosis.

Study Overview

• Status: Completed
• Conditions: Osteoporosis; Spinal Fractures
• Intervention / Treatment: Device: Percutaneous vertebroplasty; Procedure: Sham vertebroplasty

Detailed Description

Spontaneous, atraumatic compression fractures due to osteoporosis occur in more than 700,000 patients per year. Pain associated with these fractures may be excruciating, but before the advent of percutaneous vertebroplasty, treatment options were limited. Analgesic medications, bed rest, and bracing have been the mainstays of treatment, but each of these therapies has substantial limitations.

Because of the dearth of viable treatment options for osteoporotic vertebral compression fractures, the practice of percutaneous vertebroplasty, which involves injection of polymethylmethacrylate (medical cement) into the fractured vertebra, has disseminated rapidly. However, evidence for the efficacy of percutaneous vertebroplasty is currently limited to uncontrolled, nonblinded, small case studies. Even though high rates of success are reported, with up to 90% of patients achieving substantial pain relief, these case studies have not accounted for numerous important potential biases, including the natural tendency for compression fractures to heal spontaneously, regression toward the mean (wherein patients seek medical attention when pain is maximum), and the placebo effect. This study will examine the clinical efficacy of percutaneous vertebroplasty for treatment of painful osteoporotic vertebral compression fractures.

Participants in this study will be randomly assigned to receive either percutaneous vertebroplasty or a sham procedure (placebo control group). Participants may have up to 2 spinal levels treated. Participants will be enrolled in the study for 1 year and will have study visits at entry and Months 1 and 12. There will also be phone visits at Days 1, 2, 3, and 14 and Months 3 and 6. After Month 1, crossover from the placebo group to the vertebroplasty group will be allowed.

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed osteoporosis or osteopenia by a referring physician and/or medical history and physical exam OR osteopenia on plain film
• Vertebral compression fracture in vertebrae T4 through L5, of less than 1 year old
• Pain not responsive to standard medical therapy
• Current rating for pain intensity of at least 3 on a scale of 0 to 10

Exclusion Criteria:

• Evidence or suspicion of malignant tumor or spinal canal compromise
• Concomitant hip fracture
• Local or systemic infection
• Uncorrectable bleeding diatheses
• Surgery within the previous 60 days
• Lack of access to telephone
• Inability to communicate in English
• Dementia
• Pregnancy
• Abnormal renal function or anticipated venography
• Conscious sedation is contraindicated for subject

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vertebroplasty; Participants will receive percutaneous vertebroplasty	Device: Percutaneous vertebroplasty; Placement of polymethylmethacrylate (PMMA) into vertebral compression fracture
Placebo Comparator: Control Group; Participants will receive sham vertebroplasty without PMMA	Procedure: Sham vertebroplasty; Participants, following local anesthesia with lidocaine and bupivacaine, were given verbal and physical cues such as pressure on the back, but the needle was not placed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Back-specific Functional Status Using Roland-Morris Disability Questionnaire (RDQ) Scale at 1 Month	Back-specific functional status using RDQ scale range from 0 (no pain) to 23, with higher scores indicating more severe disability.	1 month after procedure
Patient's Rating of Average Pain at 1 Month	Patient's rating of average pain intensity during the preceding 24 hours at 1 month. The rating scale was from 0 to 10, with higher scores indicating more severe pain.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Well-being at 1 Month	Patient well-being was quantified by these tools: Health status outcome using Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36). Scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36), version 2. Subjects completed the SF-36 which consists of 8 sub-scales which are additionally summarized into 2 summary components (physical and mental). The subscales and the summary scales both range from 0 to 100, with (0 = worst imaginable, 100 = best imaginable). Pain Frequency Index, Pain Bothersome Index (scores range from 0-4, higher scores indicating more severe pain). European Quality of Life (QOL) 5 Dimensions (EQ-5D), scale range -0.1 to 1.0; higher scores indicating a better QOL. Study of Osteoporotic Fractures-Activities of Daily Living (SOF ADL6) range from 0 to 18; higher scores = more back-related disability.	Month 1

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: David F. Kallmes, MD, Mayo Clinic

Publications and helpful links

General Publications

• Kallmes DF, Jensen ME. Percutaneous vertebroplasty. Radiology. 2003 Oct;229(1):27-36. doi: 10.1148/radiol.2291020222.
• Kallmes DF, Comstock BA, Heagerty PJ, Turner JA, Wilson DJ, Diamond TH, Edwards R, Gray LA, Stout L, Owen S, Hollingworth W, Ghdoke B, Annesley-Williams DJ, Ralston SH, Jarvik JG. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med. 2009 Aug 6;361(6):569-79. doi: 10.1056/NEJMoa0900563. Erratum In: N Engl J Med. 2012 Mar 8;366(10):970.
• Comstock BA, Sitlani CM, Jarvik JG, Heagerty PJ, Turner JA, Kallmes DF. Investigational vertebroplasty safety and efficacy trial (INVEST): patient-reported outcomes through 1 year. Radiology. 2013 Oct;269(1):224-31. doi: 10.1148/radiol.13120821. Epub 2013 May 21.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start: April 1, 2003
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: September 10, 2003
• First Submitted That Met QC Criteria: September 10, 2003
• First Posted (Estimate): September 11, 2003

Study Record Updates

• Last Update Posted (Estimate): September 27, 2012
• Last Update Submitted That Met QC Criteria: September 24, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Back Pain; Vertebroplasty; PMMA; INVEST; Crushed Vertebrae; Structurally Unstable Vertebrae; polymethylmethacrylate; RDQ
• Additional Relevant MeSH Terms: Metabolic Diseases; Fractures, Bone; Wounds and Injuries; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Spinal Injuries; Back Injuries; Osteoporosis; Spinal Fractures
• Other Study ID Numbers: 1912-03; R01AR049373 (U.S. NIH Grant/Contract); NIAMS-096; UL1RR025014 (U.S. NIH Grant/Contract)