Vertebroplasty for the Treatment of Fractures Due to Osteoporosis

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00068822
• Collaborator: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (NIH), National Center for Research Resources (NCRR) (NIH)
• Enrollment: 131
• Location: 1
• Arms: 2
• Duration (Months): 77
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Spinal Fractures; Osteoporosis	Device: Percutaneous vertebroplasty; Procedure: Sham vertebroplasty	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Investigational Vertebroplasty Efficacy and Safety Trial (INVEST)
• Study Start Date: Apr 1, 2003
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Back-specific Functional Status Using Roland-Morris Disability Questionnaire (RDQ) Scale at 1 Month [1 month after procedure]

   Back-specific functional status using RDQ scale range from 0 (no pain) to 23, with higher scores indicating more severe disability.

2. Patient's Rating of Average Pain at 1 Month [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.

Secondary Outcome Measures

1. Patient Well-being at 1 Month [Month 1]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• 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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

• Kallmes DF, Jensen ME. Percutaneous vertebroplasty. Radiology. 2003 Oct;229(1):27-36. Review.

• ClinicalTrials.gov Identifier: NCT00068822
• Other Study ID Numbers: 1912-03; R01AR049373; NIAMS-096; UL1RR025014
• First Posted: Sep 11, 2003
• Last Update Posted: Sep 27, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by , ,: Vertebroplasty; Crushed Vertebrae; Back Pain; Structurally Unstable Vertebrae; polymethylmethacrylate; INVEST; PMMA; RDQ
• Additional relevant MeSH terms: Osteoporosis; Spinal Fractures

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at five centers in the U.S., five centers in the United Kingdom and one center in Australia.

Arm/Group Title	Vertebroplasty, Then Control	Control, Then Vertebroplasty
Arm/Group Description	Participants randomized to receive percutaneous vertebroplasty first (placement of polymethylmethacrylate [PMMA] into vertebral compression fracture). At Month 1 or Month 3 if participants did not get enough pain relief from the procedure, they could opt to crossover to the alternative Control procedure, Sham Vertebroplasty (partial vertebroplasty without PMMA in which participants were given verbal and physical cues such as pressure on the back, following local anesthesia with lidocaine and bupivacaine, but the needle was not placed.)	Participants randomized to receive Control procedure, Sham Vertebroplasty first (Partial vertebroplasty without PMMA in which participants were given verbal and physical cues such as pressure on the back, following local anesthesia with lidocaine and bupivacaine, but the needle was not placed.) At Month 1 or Month 3 if participants did not get enough pain relief from the procedure, they could opt to crossover to the alternative percutaneous vertebroplasty (placement of polymethylmethacrylate [PMMA] into vertebral compression fracture).
Period Title: First Randomized Intervention
STARTED	68	63
COMPLETED	67	61
NOT COMPLETED	1	2
Period Title: First Randomized Intervention
STARTED	9	29
Crossover at Month 1	1	2
Crossover at Month 3	8	27
COMPLETED	9	29
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Vertebroplasty	Control Group	Total
Arm/Group Description	Participants will receive percutaneous vertebroplasty	Participants will receive partial vertebroplasty without PMMA	Total of all reporting groups
Overall Participants	68	63	131
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.4 (9.4)	74.3 (9.6)	73.84 (9.48)
Sex: Female, Male (Count of Participants)
Female	53 77.9%	46 73%	99 75.6%
Male	15 22.1%	17 27%	32 24.4%
Region of Enrollment (participants) [Number]
United States	29 42.6%	28 44.4%	57 43.5%
United Kingdom	26 38.2%	26 41.3%	52 39.7%
Australia	13 19.1%	9 14.3%	22 16.8%
RDQ Score at baseline (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	16.6 (3.8)	17.5 (4.1)	17.05 (3.98)
Average pain intensity during past 24 hours at baseline (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	6.9 (2.0)	7.2 (1.8)	7.02 (1.9)
SF-36 score; summary physical component at baseline (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	25.3 (7.8)	25.3 (7.3)	25.3 (7.55)
SF-36 score; summary mental component at baseline (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	44.8 (11.8)	41.5 (14.1)	43.21 (13.03)
Pain Frequency Index Score at baseline (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	3.0 (0.8)	3.1 (0.8)	3.04 (0.8)
Pain Bothersome Index score at baseline (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	2.9 (0.7)	3.1 (0.8)	2.98 (0.75)
EQ-SD Score at baseline (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	0.57 (0.18)	0.54 (0.23)	0.55 (0.20)
SOF-ADL Score at baseline (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	10.0 (3.6)	10.3 (2.8)	10.14 (3.23)

Outcome Measures

1. Primary Outcome

Title	Back-specific Functional Status Using Roland-Morris Disability Questionnaire (RDQ) Scale at 1 Month
Description	Back-specific functional status using RDQ scale range from 0 (no pain) to 23, with higher scores indicating more severe disability.
Time Frame	1 month after procedure

Outcome Measure Data

Analysis Population Description

68 subjects were randomized to undergo vertebroplasty and 63 to undergo the control intervention. All underwent the assigned intervention. One subject in the vertebroplasty group and two subjects in the control group were lost to follow-up before 1 month.

Arm/Group Title	Vertebroplasty	Control Group
Arm/Group Description	Participants will receive percutaneous vertebroplasty	Participants will receive partial vertebroplasty without PMMA
Measure Participants	67	61
Mean (Standard Deviation) [units on a scale]	12.0 (6.3)	13.0 (6.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vertebroplasty, Control Group
	Comments	Between group comparisons, confidence intervals, and P values were calculated with the use of analysis-of-covariance models with adjustment for study group assignment, baseline value of the outcome measure, and study center. Negative treatment effects favor the control procedure, and positive treatment effects favor vertebroplasty.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted treatment effect
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -1.3 to 2.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Patient Well-being at 1 Month
Description	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.
Time Frame	Month 1

Outcome Measure Data

Analysis Population Description

68 subjects were randomized to undergo vertebroplasty and 63 to undergo the control intervention. All underwent the assigned intervention. One subject in the vertebroplasty group and two subjects in the control group were lost to follow-up before 1 month.

Arm/Group Title	Vertebroplasty	Control Group
Arm/Group Description	Participants will receive percutaneous vertebroplasty	Participants will receive partial vertebroplasty without PMMA
Measure Participants	67	61
SF-36 summary physical component	29.7 (9.6)	28.7 (8.0)
SF-36 summary mental component	46.9 (12.0)	45.6 (14.8)
Pain frequency index score	2.1 (1.2)	2.3 (1.1)
Pain bothersome index score	1.9 (1.1)	2.1 (1.1)
EQ-5D score	0.70 (0.18)	0.64 (0.20)
SOF-ADL score	7.7 (3.7)	8.2 (3.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vertebroplasty, Control Group
	Comments	SF-36 Physical Component Summary treatment effect
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -1.7 to 3.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vertebroplasty, Control Group
	Comments	SF-36 Mental Component Summary treatment effect
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -3.7 to 4.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vertebroplasty, Control Group
	Comments	Pain Frequency Index treatment effect
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.2 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vertebroplasty, Control Group
	Comments	Pain Bothersome Index treatment effect
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.33
	Confidence Interval	(2-Sided) 95%; -0.2 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Vertebroplasty, Control Group
	Comments	EQ-5D Index treatment effect
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Vertebroplasty, Control Group
	Comments	SOF-ADL treatment effect
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment Effect
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.8 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Patient's Rating of Average Pain at 1 Month
Description	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.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

68 subjects were randomized to undergo vertebroplasty and 63 to undergo the control intervention. All underwent the assigned intervention. One subject in the vertebroplasty group and two subjects in the control group were lost to follow-up before 1 month.

Arm/Group Title	Vertebroplasty	Control Group
Arm/Group Description	Participants will receive percutaneous vertebroplasty	Participants will receive partial vertebroplasty without PMMA
Measure Participants	67	61
Mean (Standard Deviation) [units on a scale]	3.9 (2.9)	4.6 (3.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vertebroplasty, Control Group
	Comments	Between group comparisons, confidence intervals, and P values were calculated with the use of analysis-of-covariance models with adjustment for study group assignment, baseline value of the outcome measure, and study center. Negative treatment effects favor the control procedure, and positive treatment effects favor vertebroplasty.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted treatment effect
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -0.3 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	12 months from baseline
Arm/Group Title	Vertebroplasty		Control Group
Arm/Group Description	Participants will receive percutaneous vertebroplasty		Participants will receive partial vertebroplasty without PMMA
All Cause Mortality
	Vertebroplasty		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vertebroplasty		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/68 (1.5%)		1/61 (1.6%)
Cardiac disorders
Tachycardia and rigors	0/68 (0%)	0	1/61 (1.6%)	1
Injury, poisoning and procedural complications
Surgical injury	1/68 (1.5%)	1	0/61 (0%)	0
Other (Not Including Serious) Adverse Events
	Vertebroplasty		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/61 (0%)

Limitations/Caveats

The possible role of the placebo effect on outcomes remains unclear. Crossover at 1 month was allowed, which complicated the interpretation of between-group outcome differences. Other medical treatments received were not compared to study groups.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.