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Effects of Etanercept on the Heart, Veins and Thickness of Certain Major Arteries In Ankylosing Spondylitis Patients (CREST)

This study has been terminated.
Sponsor:
Collaborator:
Lincoln Medical and Mental Health Center
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00910273
First received: May 27, 2009
Last updated: December 8, 2015
Last verified: December 2015
  Purpose
Study to assess whether etanercept therapy is able to increase flow-mediated vasodilatation in AS, and whether etanercept can modify the intima-media thickness (IMT) in these patients

Condition Intervention Phase
Ankylosing Spondylitis
Drug: etanercept
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Etanercept on Endothelial Function and Carotid Intima-media Thickness (IMT) in Patients With Active AS

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change From Baseline in Flow-Mediated Dilatation (FMD) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Brachial artery (BA) FMD equals (=)(maximum diameter minus[-] baseline diameter divided by baseline diameter) times (*) 100 percent (%). Ultrasound images of BA at rest were followed by blood pressure (BP) cuff inflated to at least 50 millimeters of mercury (mm Hg) above participants systolic BP for 5 minutes. Cuff released and reactive hyperaemia was produced. BA was imaged continuously from 30 seconds prior cuff inflation to 2 minutes after cuff deflation. Higher scores indicate improved endothelial function.


Secondary Outcome Measures:
  • Change From Baseline in Flow-Mediated Dilatation at Weeks 4, 24, 36, and 52 [ Time Frame: Baseline, Weeks 4, 24, 36, and 52 or Early Termination (ET) ] [ Designated as safety issue: Yes ]
    BA FMD =(maximum diameter -baseline diameter divided by baseline diameter) * 100%. Ultrasound images of BA at rest were followed by BP cuff inflated to at least 50 mm Hg above participants systolic BP for 5 minutes. Cuff released and reactive hyperaemia was produced. BA was imaged continuously from 30 seconds prior cuff inflation to 2 minutes after cuff deflation. Higher scores indicate improved endothelial function. Change: Week x observation minus Baseline observation.

  • Change From Baseline in Carotid Intima Media Thickness (IMT) at Weeks 12 and 52 [ Time Frame: Baseline, Week 12 and 52 or ET ] [ Designated as safety issue: Yes ]
    Change in IMT in the distal common carotid arteries (CCA), common bulbs (CB), and internal carotid arteries (ICA) as determined by ultrasound. Higher scores indicate worsening in cardiovascular risk assessment. Change: Week x observation minus Baseline observation.

  • Change From Baseline Lipid Parameters at Weeks 4, 12, 24, 36 and 52 [ Time Frame: Baseline, Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    Mean Total Cholesterol (TC), Low Density Lipoprotein (LDL) and Triglyceride (TGL) blood concentrations, lower values indicated improvement in cardiovascular risk. Mean High Density Lipoprotein (HDL), higher values indicated improvement in cardiovascular risk. Change: Week x observation minus Baseline observation. Baseline value was used when present, otherwise valid screening value used as baseline if within 14 days of first test article injection.

  • Change From Baseline in Total Serum Homocysteine at Weeks 4, 12, 24, 36 and 52 [ Time Frame: Baseline, Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    Mean serum homocysteine blood concentrations. Lower values of homocysteine indicate improvement in inflammation. Change: Week x observation minus Baseline observation. Baseline value was used when present, otherwise valid screening value used as baseline if within 14 days of first test article injection.

  • Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Weeks 4, 12, 24, 36 and 52 [ Time Frame: Baseline, Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hour (hr). A higher rate is consistent with inflammation. Change: Week x observation minus Baseline observation. Baseline value was used when present, otherwise valid screening value used as baseline if within 14 days of first test article injection.

  • Change From Baseline in C-Reactive Protein (CRP) at Weeks 4, 12, 24, 36, 52 [ Time Frame: Baseline, Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. Change: Week x observation minus Baseline observation. Baseline value was used when present, otherwise valid screening value used as baseline if within 14 days of first test article injection.

  • Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 4, 12, 24, 36 and 52 [ Time Frame: Baseline, Weeks 4, 12, 24, 36, and 52 or ET ] [ Designated as safety issue: No ]
    BASDAI a validated self assessment tool to determine disease activity in participant with Ankylosing Spondylitis (AS) using a Visual Analog Scale (VAS) of 0 (none) to 10 (very severe) centimeter (cm). Participant answered 6 questions measuring discomfort, pain and fatigue. Final BASDAI score averages the individual assessments for a final score range of 0-10. Change: Week x observation minus Baseline observation. Higher score indicates greater disability. Baseline value was used when present, otherwise valid screening value used as baseline if within 14 days of first test article injection.

  • Percentage of Participants With BASDAI 50 Percent (%) Improvement at Weeks 4, 12, 24, 36, and 52 [ Time Frame: Weeks 4, 12, 24, 36, and 52 or ET ] [ Designated as safety issue: No ]
    BASDAI a validated self assessment tool used to determine disease activity in participants with AS. Utilizing a VAS of 0 (none) to 10 cm (very severe), participant's answered 6 questions measuring discomfort, pain and fatigue. BASDAI 50 response defined as at least a 50% improvement (decrease) from baseline in BASDAI. Baseline score - score at observation divided by Baseline score * 100 = greater than or equal to 50%.

  • Percentage of Participants With Assessment in Ankylosing Spondylitis (ASAS) 20 at Weeks 4, 12, 24, 36, and 52 [ Time Frame: Week 4, 12, 24, 36, and 52 or ET ] [ Designated as safety issue: No ]
    ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) participants ASAS = 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 20 = 20% improvement from baseline and an absolute change greater than or equal to (≥) 10 units on a 0-100 millimeter (mm) scale (0 mm = no disease activity; 100 mm = high disease activity) for ≥ 3 domains, and no worsening in remaining domain.

  • Percentage of Participants With ASAS 40 at Weeks 4, 12, 24, 36, and 52 [ Time Frame: Weeks 4, 12, 24, 36, and 52 or ET ] [ Designated as safety issue: No ]
    ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) participants ASAS = 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 40 = 40% improvement from baseline and an absolute change ≥ 20 units on a 0-100 mm scale (0 mm = no disease activity, 100 mm = high disease activity) for ≥ 3 domains, and no worsening in remaining domain.

  • Percentage of Participants With ASAS 50 at Weeks 4, 12, 24, 36, and 52 [ Time Frame: Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) participants ASAS = 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 50 = 50% improvement (vs. baseline) and an absolute change ≥ 20 units on a 0-100 mm scale (0 mm = no disease activity, 100 mm = high disease activity) for ≥ 3 domains, and no worsening in remaining domain.

  • Percentage of Participants With ASAS 70 at Weeks 4, 12, 24, 36, and 52 [ Time Frame: Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) participants ASAS = 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 70 = 70% improvement (vs. baseline) and an absolute change ≥ 20 units on a 0-100 mm scale (0 mm = no disease activity, 100 mm = high disease activity) for ≥ 3 domains, and no worsening in remaining domain.

  • Percentage of Participants With ASAS 5/6 at Weeks 4, 12, 24, 36, and 52 [ Time Frame: Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    ASAS 5/6 consists of 6 domains: the 4 used in ASAS 20 (participant global assessment of disease activity, pain, function, inflammation measured on a 0-100 scale, where 0 = no disease activity and 100=high disease activity) plus spinal mobility and an acute phase reactant, C Reactive Protein (CRP). Achieving ASAS 5/6 requires a 20% improvement compared to baseline in ≥ 5 domains and no worsening in the remaining domain.

  • Percentage of Participants With ASAS Partial Remission at Weeks 4, 12, 24, 36, and 52 [ Time Frame: Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    Partial remission defined as a score of less than 20 units (on a scale of 0-100, where 0 = no disease activity and 100 = high disease activity) in each of the 4 Assessment in Ankylosing Spondylitis (ASAS) domains: participant global assessment of disease activity, pain, function, and inflammation. For scale, 100=high disease activity.

  • Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 4, 12, 24, 36, and 52 [ Time Frame: Baseline, Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: cervical rotation, intermalleolar distance, modified Schober's test, lateral flexion and tragus to wall distance. Each measure was scored 0-2 (0=normal mobility, 2=severe reduction) to give a final score ranging 0 to 10. Lower score indicated better spinal mobility. Change: Week x observation minus Baseline observation. Baseline value was used when present, otherwise valid screening value used as baseline if within 14 days of first test article injection.

  • Change From Baseline in BASMI-Cervical Rotation at Weeks 4, 12, 24, 36 and 52 [ Time Frame: Baseline, Weeks 4, 12, 24, 36, 52 or ET ] [ Designated as safety issue: No ]
    While in a neutral position, the participant turned the head as far as possible to the right and then to the left. Using a goniometer the degrees of movement were measured. Two measurements on the right and 2 on the left were made. The best of the two measurements for each side (corresponding to the highest value), were then averaged. Higher score indicated greater spinal mobility. Actual rotation ranged from 3.0 to 99.0 degrees. Change: Week x observation minus Baseline observation. Baseline value was used when present, otherwise valid screening value used as baseline if within 14 days of first test article injection.

  • Change From Baseline in BASMI-Intermalleolar Distance at Weeks 4, 12, 24, 36 and 52 [ Time Frame: Baseline, Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    Measurement in cm of the distance between the medial malleoli when participant was lying supine with knees straight and feet pointed straight up with legs separated as far as possible, 2 attempts were measured. The best of the two measurements which corresponds to the highest value were reported. Higher score indicated greater spinal mobility. Change: Week x observation minus Baseline observation. Baseline value was used when present, otherwise valid screening value used as baseline if within 14 days of first test article injection.

  • Change From Baseline in BASMI-Modified Schober's Test at Weeks 4, 12, 24, 36 and 52 [ Time Frame: Baseline, Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    Measurement in cm of distance between marks originally placed while participant was standing erect 10 cm above and 5 cm below the midpoint of a line that joins the posterior superior iliac spines. Distance between marks was re-measured with participant maximally bent forward, knees fully extended, with supine in full flexion. The measurement was carried out two times and best of the two measurements which corresponds to the highest value were reported. Higher score indicated greater spinal mobility. Change: Week x observation minus Baseline observation. Baseline value was used when present, otherwise valid screening value used as baseline if within 14 days of first test article injection.

  • Change From Baseline in BASMI-Tragus to Wall Distance at Weeks 4, 12, 24, 36 and 52 [ Time Frame: Baseline, Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    Measurement in cm of distance between the tragus and wall from the right and left side while participant was standing with back against the wall; knees straight; scapulae, buttocks, and heels against the wall; with head in a neutral position. Two measurements on the right and 2 on the left were made. The best of the two measurements for each side (corresponding to the smallest value), were then averaged. Higher score indicated greater spinal mobility. Change: Week x observation minus Baseline observation. Baseline value was used when present, otherwise valid screening value used as baseline if within 14 days of first test article injection.

  • Change From Baseline in BASMI-Lateral Flexion at Weeks 4, 12, 24, 36 and 52 [ Time Frame: Baseline, Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    Measurement in cm of distance between participant's middle fingertip and the floor after bending sideways, without bending knees or lifting heels, while attempting to keep shoulders in same place (flexion position). Two measurements on the right and 2 on the left were made. The best of the two measurements for each side (corresponding to the highest value), were then averaged. Higher score indicated greater spinal mobility. Change: Week x observation minus Baseline observation. Baseline value was used when present, otherwise valid screening value used as baseline if within 14 days of first test article injection.

  • Change From Baseline in Occiput-to-Wall Distance at Weeks 4, 12, 24, 36 and 52 [ Time Frame: Baseline, Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    While participant stood with back against the wall and during maximal effort to touch head to the wall, the distance between the occiput (back of head) and the wall was measured. The measurement of two attempts was made and best of the two measurements which corresponds to the highest value were reported. Lower scores indicated improvement in spinal mobility. Change: Week x observation minus Baseline observation. Baseline value was used when present, otherwise valid screening value used as baseline if within 14 days of first test article injection.

  • Change From Baseline in Chest Expansion at Weeks 4, 12, 24, 36 and 52 [ Time Frame: Baseline, Weeks 4, 12, 24, 36 and 52 or ET ] [ Designated as safety issue: No ]
    Chest expansion defined as the difference in thoracic circumference during full expiration versus full inspiration, measured in cm at the fourth intercostal space (nipple line) while participant was standing. Measurement taken twice and best of the two measurements (corresponding to the highest value of inspiration and smallest value for expiration), were then averaged. Greater chest circumference indicated improvement in spinal mobility. Change: Week x observation minus Baseline observation. Baseline value was used when present, otherwise valid screening value used as baseline if within 14 days of first test article injection.


Enrollment: 34
Study Start Date: July 2009
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
etanercept 50 mg/week
Drug: etanercept
etanercept 50 mg/week
Other Name: Enbrel

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of AS, as defined by Modified New York Criteria for Ankylosing Spondylitis.
  2. AS with active disease as defined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI, see Attachment 4) >= 4 at screening visit.
  3. Patients capable, in the opinion of the investigator, of complying with the treatment schedule and doses throughout the 52 weeks
  4. Agreement by male subjects who are not surgically sterile and female subjects who are not surgically sterile or postmenopausal to use reliable methods of birth control for the duration of the study.
  5. Ability to self-inject drug or have a designee who can do so.
  6. Ability to store injectable test article at 2ºC to 8ºC.

Exclusion Criteria:

1. Pregnancy confirmed by test taken at screening in all women except those who were surgically sterile or at least 1 year postmenopausal. Sexually active women of childbearing potential participating in the study must use a medically acceptable form of contraception that needs to be continued for 15 days following discontinuation of the test article.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00910273

Locations
Italy
Pfizer Investigational Site
Bologna, Italy, 40138
Pfizer Investigational Site
Prato, Italy, 59100
Pfizer Investigational Site
Reggio Emilia, Italy, 42100
Pfizer Investigational Site
Roma, Italy, 00161
Sponsors and Collaborators
Pfizer
Lincoln Medical and Mental Health Center
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00910273     History of Changes
Other Study ID Numbers: 0881A3-4458 
Study First Received: May 27, 2009
Results First Received: October 3, 2012
Last Updated: December 8, 2015
Health Authority: Italy: Ethics Committee

Keywords provided by Pfizer:
IMT evaluation in AS patients treated with etanercept

Additional relevant MeSH terms:
Spondylitis
Spondylitis, Ankylosing
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Spondylarthritis
Ankylosis
Joint Diseases
Arthritis
Etanercept
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 30, 2016