Back to resultsEffects of Nonsteroidal Anti-Inflammatory Drugs in Recurrence of Spondyloarthritis Patients After Remission
Primary Purpose
Axial Spondyloarthritis
Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
To withdraw NSAIDs therapy
To continue NSAIDs therapy
Sponsored by
About this trial
This is an interventional treatment trial for Axial Spondyloarthritis focused on measuring Axial Spondyloarthritis, Anti-Inflammatory Drugs, Flare
Eligibility Criteria
Inclusion Criteria:
- Capable of giving informed consent and complying with the examination program of the protocol;
- Participants with axial SpA fulfilling the Assessment of Spondyloarthritis international Society 2009 (ASAS) axial SpA classification criteria;
- Participants must fulfill the criteria of maintaining remission of aSpA, defined as ASDAS<1.3；
- Participants must fulfill the criteria of remission of aSpA defined as ASDAS<1.3，then continuous to evaluate every four weeks for three times and ASDAS<1.3 each time.
- Laboratory results must fulfill following requirements: Hb≥85g/L；3.5×109/L≤WBC Count ≤10×109/L；Platelet count ≥ Normal lower limit; Liver function (ALT、TBIL) ≤Twofold of normal upper limit; Renal function (SCr) ≤Normal upper limit;
- The pregnancy test must be negative for women of childbearing age; Efficient contraception must be taken for both male and female participants during the trial period and within three months after the end of the trial.
Exclusion Criteria:
- Participants who previously have experienced allergic reactions to NSAIDs or sulfa-drugs;
- Participants who are intolerant of NSAIDs;
- Participants who are in active axSpA episodes;
- Participants with previous or currant ulcers and/or gastrointestinal conditions or bleeding in three months
- Participants who were in acute infection or acute attack of chronic infection during screening period;
- At the time of screening, participants who were in the acute stage of acute infection or chronic infection, and if the acute infection had improved, they could be re-screened.
- Participants who suffer from invasive fungal infections (e.g. histoplasma, coccidiosis's, candida, aspergillus, blastomyces, pneumocystis, etc.) within the first 6 months of screening; Or opportunistic bacterial infections (e.g. bacterial, viral or other infections, including Legionella and Listeria);
- Participants with other autoimmune diseases which are expected to influence the evaluation of experimental medications, such as inflammatory enteritis, psoriasis, uveitis, etc.
- Participants with previous or currant congestive heart failure, coronary heart disease, serious arrhythmia;
- Participants with severe, progressive, uncontrolled vital organ and systematic disorders, and other conditions that are considered inappropriate to participate in this trial;
- Participants with circumstances that may affect the compliance (e.g. prolonged travel or leave, planned relocation, mental illness, lack of motivation to participate, etc.).
Sites / Locations
- The First Affiliated Hospital of Xiamen UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Non- NSAIDS group
NSAIDS group
Arm Description
To withdraw NSAIDS therapy
To continue NSAIDS therapy
Outcomes
Primary Outcome Measures
Percentage of participants with Ankylosing Spondylitis Disease Activity Score (ASDAS) active disease
ASDAS active disease is defined as ΔASDAS-CRP≥0.9. The ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation.
Secondary Outcome Measures
Change in Patient global assessment of disease activity
Participant rated instrument to measure participants' global assessment of disease activity on a 10 cm visual analogue scale, ranging from no activity to highest possible activity.
Change in total Back Pain
Participants assessed the total back pain they had in the previous 1 week on a scale from 0 (no pain) to 10 (most severe pain).
Change in Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
A numeric rating scale was used, for questions 1-5 (Fatigue, Spinal Pain, Joint pain or Swelling, Discomfort and Morning stiffness severity respectively) on a scale from 0 (none) to 10 (very severe). Question 6 (morning stiffness duration) was recorded on a scale of 0 (0 or more hours) to 10 (2 hours). To give the five major Ankylosing Spondylitis (AS) symptoms equal weighting, the average of the two scores relating to morning stiffness was taken. This averaged morning stiffness score was then summed with the remaining 4 questions, resulting in a composite score on a scale of 0-50, which was then divided by 5 to give the final BASDAI score on a scale of 0-10.
Change in Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
The BASFI is a participant's self-assessment represented as a mean (VAS; 0 to 10) of 10 questions, 8 of which relate to the participant's functional anatomy and 2 of which relate to a participant's ability to cope with everyday life. An increase along the scale indicates a worsening condition.
Change in Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
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.
Change in Short Form-36 Physical Component Summary (SF-36 PCS)
The change from Baseline in Short Form-36 Physical Component Summary (SF-36 PCS)
Change in European Quality of Life-5 Dimensions (EQ-5D) Questionnaire
The EQ-5D is an international, standardized, generic instrument for describing and valuing health status.In description part, health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In evaluation part, the respondents evaluate their overall health status using the visual analogue scale (EQ-VAS).Visual analogue scale is the second part of the questionnaire, asking to mark health status on the day of the interview on a 20 cm vertical scale with end points of 0 and 100. There are notes at the both ends of the scale that the bottom rate (0) corresponds to " the worst health you can imagine", and the highest rate (100) corresponds to "the best health you can imagine".
Change in Chest Expansion
Chest expansion, measured in cm, is defined as the difference in thoracic circumference during full expiration versus full inspiration, measured at the fourth intercostal space (nipple line). Chest expansion was measured for both maximum and minimum inhalation and the data presented below combined both the values.
Change in Maastricht Ankylosing Spondylitis Enthesitis Index (MASES)
The MASES evaluation will be conducted at the designated study visits to assess the presence or absence of enthesitis at 13 different sites, noting the subjects' responses.
Change in Number of swelling and tendons affected by enthesitis
An assessment of 44 swelling joints and 46 tendons joints will be done by physical examination at the designated study visits. Joint swelling will be classified as present (1), absent (0), replaced (9), or no assessment (NA).
Change in Blood samples: C-reactive protein (CRP) and Erythrocyte sedimentation rate(ESR)
General and specific markers of inflammation. ESR will be evaluated at the site and expressed in mm/hg (1st hour).
Observation of relapse time after withdrawal of NSAIDs in remission patients
ASDAS active disease is defined as ΔASDAS-CRP≥0.9
The difference of flare rate between different treatment groups
ASDAS active disease is defined as ΔASDAS-CRP≥0.9
The difference of flare rate between in patients with different sacroiliac joint grades on X-ray among different groups.
To grade radiographic sacroiliitis according to the New York criteria: grade0 normal; grade1 suspicious; grade2 minimal sacroiliitis; grade3 moderate sacroiliitis; grade4 ankylosis.
The difference of osteophyte formation between different groups on Modified Stoke ankylosing spondylitis spine score (mSASSS).
mSASSS focuses on the anterior vertebral body angles from the lower T12 endplate to the upper S1 endplate on a lateral radiograph. Each angle is scored 0 (normal), 1 (shiny corner sign, squaring, or sclerosis), 2 (enthesophyte), or 3 (bridging), so that the total score can range from 0 to 72.
Comparison of BASFI and BASMI scores between different groups
The BASFI is a participant's self-assessment represented as a mean (VAS; 0 to 10) of 10 questions, 8 of which relate to the participant's functional anatomy and 2 of which relate to a participant's ability to cope with everyday life. An increase along the scale indicates a worsening condition. 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.
Differences in MRI scores among different groups by SPARCC SSS method.
The SPARCC SSS method was developed based on semicoronal T1WSE sequences of the sacroiliac joints (SIJ). The transitional slice is identified by scrolling from anterior to posterior through the SIJ and viewing DICOM images depicting semicoronal slices through the joint. Scoring ranges are fat metaplasia (0-40), erosion (0-40), backfill (0-20), and ankylosis (0-20).
The difference of flare rate in patients with different MRI scores of sacroiliac joint.
MRI scores are measured by SPARCC SSS method.
Full Information
NCT ID
NCT03425812
First Posted
January 19, 2018
Last Updated
April 11, 2022
Sponsor
The First Affiliated Hospital of Xiamen University
Collaborators
First Affiliated Hospital of Fujian Medical University, Peking University Shenzhen Hospital, Zhangzhou Affiliated Hospital of Fujian Medical University, Quanzhou Orthopedic-traumatological Hospital of Fujian Traditional Chinese Medicine University, Fujian Medical University Union Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03425812
Brief Title
Effects of Nonsteroidal Anti-Inflammatory Drugs in Recurrence of Spondyloarthritis Patients After Remission
Official Title
Effects of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in Recurrence of Spondyloarthritis (SPA) Patients After Remission：A Multicenter, Randomized, Controlled Study
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 15, 2018 (Actual)
Primary Completion Date
December 20, 2025 (Anticipated)
Study Completion Date
December 20, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital of Xiamen University
Collaborators
First Affiliated Hospital of Fujian Medical University, Peking University Shenzhen Hospital, Zhangzhou Affiliated Hospital of Fujian Medical University, Quanzhou Orthopedic-traumatological Hospital of Fujian Traditional Chinese Medicine University, Fujian Medical University Union Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The multicenter, randomized controlled trial is to investigate and evaluate the effect of NSAIDs therapy on recurrence in patients with axial spondyloarthritis;
Detailed Description
To investigate the recurrence rate in remission patients who withdraw NSAIDs therapy in axial spondyloarthritis;
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Axial Spondyloarthritis
Keywords
Axial Spondyloarthritis, Anti-Inflammatory Drugs, Flare
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
140 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Non- NSAIDS group
Arm Type
Experimental
Arm Description
To withdraw NSAIDS therapy
Arm Title
NSAIDS group
Arm Type
Active Comparator
Arm Description
To continue NSAIDS therapy
Intervention Type
Drug
Intervention Name(s)
To withdraw NSAIDs therapy
Other Intervention Name(s)
Non-NSAIDs, Break-off (on-demand) NSAID therapy, Break-off NSAID use (on-demand) group
Intervention Description
NSAIDs therapy will be withdrew after washout period.
Intervention Type
Drug
Intervention Name(s)
To continue NSAIDs therapy
Other Intervention Name(s)
NSAIDs, Regular (continuous) NSAID therapy, Regular (continuous) group
Intervention Description
NSAIDs therapy will be continued.
Primary Outcome Measure Information:
Title
Percentage of participants with Ankylosing Spondylitis Disease Activity Score (ASDAS) active disease
Description
ASDAS active disease is defined as ΔASDAS-CRP≥0.9. The ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation.
Time Frame
From Week 0 (baseline) to Week24
Secondary Outcome Measure Information:
Title
Change in Patient global assessment of disease activity
Description
Participant rated instrument to measure participants' global assessment of disease activity on a 10 cm visual analogue scale, ranging from no activity to highest possible activity.
Time Frame
From Week 0 (baseline) to Week24
Title
Change in total Back Pain
Description
Participants assessed the total back pain they had in the previous 1 week on a scale from 0 (no pain) to 10 (most severe pain).
Time Frame
From Week 0 (baseline) to Week24
Title
Change in Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
Description
A numeric rating scale was used, for questions 1-5 (Fatigue, Spinal Pain, Joint pain or Swelling, Discomfort and Morning stiffness severity respectively) on a scale from 0 (none) to 10 (very severe). Question 6 (morning stiffness duration) was recorded on a scale of 0 (0 or more hours) to 10 (2 hours). To give the five major Ankylosing Spondylitis (AS) symptoms equal weighting, the average of the two scores relating to morning stiffness was taken. This averaged morning stiffness score was then summed with the remaining 4 questions, resulting in a composite score on a scale of 0-50, which was then divided by 5 to give the final BASDAI score on a scale of 0-10.
Time Frame
From Week 0 (baseline) to Week24
Title
Change in Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
Description
The BASFI is a participant's self-assessment represented as a mean (VAS; 0 to 10) of 10 questions, 8 of which relate to the participant's functional anatomy and 2 of which relate to a participant's ability to cope with everyday life. An increase along the scale indicates a worsening condition.
Time Frame
From Week 0 (baseline) to Week24
Title
Change in Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
Description
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.
Time Frame
From Week 0 (baseline) to Week24
Title
Change in Short Form-36 Physical Component Summary (SF-36 PCS)
Description
The change from Baseline in Short Form-36 Physical Component Summary (SF-36 PCS)
Time Frame
From Week 0 (baseline) to Week24
Title
Change in European Quality of Life-5 Dimensions (EQ-5D) Questionnaire
Description
The EQ-5D is an international, standardized, generic instrument for describing and valuing health status.In description part, health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In evaluation part, the respondents evaluate their overall health status using the visual analogue scale (EQ-VAS).Visual analogue scale is the second part of the questionnaire, asking to mark health status on the day of the interview on a 20 cm vertical scale with end points of 0 and 100. There are notes at the both ends of the scale that the bottom rate (0) corresponds to " the worst health you can imagine", and the highest rate (100) corresponds to "the best health you can imagine".
Time Frame
From Week 0 (baseline) to Week24
Title
Change in Chest Expansion
Description
Chest expansion, measured in cm, is defined as the difference in thoracic circumference during full expiration versus full inspiration, measured at the fourth intercostal space (nipple line). Chest expansion was measured for both maximum and minimum inhalation and the data presented below combined both the values.
Time Frame
From Week 0 (baseline) to Week24
Title
Change in Maastricht Ankylosing Spondylitis Enthesitis Index (MASES)
Description
The MASES evaluation will be conducted at the designated study visits to assess the presence or absence of enthesitis at 13 different sites, noting the subjects' responses.
Time Frame
From Week 0 (baseline) to Week24
Title
Change in Number of swelling and tendons affected by enthesitis
Description
An assessment of 44 swelling joints and 46 tendons joints will be done by physical examination at the designated study visits. Joint swelling will be classified as present (1), absent (0), replaced (9), or no assessment (NA).
Time Frame
From Week 0 (baseline) to Week24
Title
Change in Blood samples: C-reactive protein (CRP) and Erythrocyte sedimentation rate(ESR)
Description
General and specific markers of inflammation. ESR will be evaluated at the site and expressed in mm/hg (1st hour).
Time Frame
From Week 0 (baseline) to Week24
Title
Observation of relapse time after withdrawal of NSAIDs in remission patients
Description
ASDAS active disease is defined as ΔASDAS-CRP≥0.9
Time Frame
From Week 0 (baseline) to Week24
Title
The difference of flare rate between different treatment groups
Description
ASDAS active disease is defined as ΔASDAS-CRP≥0.9
Time Frame
Week12 and Week24
Title
The difference of flare rate between in patients with different sacroiliac joint grades on X-ray among different groups.
Description
To grade radiographic sacroiliitis according to the New York criteria: grade0 normal; grade1 suspicious; grade2 minimal sacroiliitis; grade3 moderate sacroiliitis; grade4 ankylosis.
Time Frame
Week12 and Week24
Title
The difference of osteophyte formation between different groups on Modified Stoke ankylosing spondylitis spine score (mSASSS).
Description
mSASSS focuses on the anterior vertebral body angles from the lower T12 endplate to the upper S1 endplate on a lateral radiograph. Each angle is scored 0 (normal), 1 (shiny corner sign, squaring, or sclerosis), 2 (enthesophyte), or 3 (bridging), so that the total score can range from 0 to 72.
Time Frame
Week0 and Week24
Title
Comparison of BASFI and BASMI scores between different groups
Description
The BASFI is a participant's self-assessment represented as a mean (VAS; 0 to 10) of 10 questions, 8 of which relate to the participant's functional anatomy and 2 of which relate to a participant's ability to cope with everyday life. An increase along the scale indicates a worsening condition. 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.
Time Frame
Week12 and Week24
Title
Differences in MRI scores among different groups by SPARCC SSS method.
Description
The SPARCC SSS method was developed based on semicoronal T1WSE sequences of the sacroiliac joints (SIJ). The transitional slice is identified by scrolling from anterior to posterior through the SIJ and viewing DICOM images depicting semicoronal slices through the joint. Scoring ranges are fat metaplasia (0-40), erosion (0-40), backfill (0-20), and ankylosis (0-20).
Time Frame
weeks-16, week 0, week 12 and week 24
Title
The difference of flare rate in patients with different MRI scores of sacroiliac joint.
Description
MRI scores are measured by SPARCC SSS method.
Time Frame
Week0 and Week24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Capable of giving informed consent and complying with the examination program of the protocol;
Participants with axial SpA fulfilling the Assessment of Spondyloarthritis international Society 2009 (ASAS) axial SpA classification criteria;
Participants must fulfill the criteria of maintaining remission of aSpA, defined as ASDAS<1.3；
Participants must fulfill the criteria of remission of aSpA defined as ASDAS<1.3，then continuous to evaluate every four weeks for three times and ASDAS<1.3 each time.
Laboratory results must fulfill following requirements: Hb≥85g/L；3.5×109/L≤WBC Count ≤10×109/L；Platelet count ≥ Normal lower limit; Liver function (ALT、TBIL) ≤Twofold of normal upper limit; Renal function (SCr) ≤Normal upper limit;
The pregnancy test must be negative for women of childbearing age; Efficient contraception must be taken for both male and female participants during the trial period and within three months after the end of the trial.
Exclusion Criteria:
Participants who previously have experienced allergic reactions to NSAIDs or sulfa-drugs;
Participants who are intolerant of NSAIDs;
Participants who are in active axSpA episodes;
Participants with previous or currant ulcers and/or gastrointestinal conditions or bleeding in three months
Participants who were in acute infection or acute attack of chronic infection during screening period;
At the time of screening, participants who were in the acute stage of acute infection or chronic infection, and if the acute infection had improved, they could be re-screened.
Participants who suffer from invasive fungal infections (e.g. histoplasma, coccidiosis's, candida, aspergillus, blastomyces, pneumocystis, etc.) within the first 6 months of screening; Or opportunistic bacterial infections (e.g. bacterial, viral or other infections, including Legionella and Listeria);
Participants with other autoimmune diseases which are expected to influence the evaluation of experimental medications, such as inflammatory enteritis, psoriasis, uveitis, etc.
Participants with previous or currant congestive heart failure, coronary heart disease, serious arrhythmia;
Participants with severe, progressive, uncontrolled vital organ and systematic disorders, and other conditions that are considered inappropriate to participate in this trial;
Participants with circumstances that may affect the compliance (e.g. prolonged travel or leave, planned relocation, mental illness, lack of motivation to participate, etc.).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shi Guixiu, PhD
Phone
86-0592-13600932661
Email
Gshi@xmu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Zheng Qing, PhD
Phone
86-0591-18650383162
Email
drmichaelzheng@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shi Guixiu, PhD
Organizational Affiliation
The First Affiliated Hospital of Xiamen University
Official's Role
Study Director
Facility Information:
Facility Name
The First Affiliated Hospital of Xiamen University
City
Xiamen
State/Province
Fujian
ZIP/Postal Code
361003
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shi Guixiu, PhD
Phone
13600932661
Email
Gshi@xmu.edu.cn
First Name & Middle Initial & Last Name & Degree
Zheng Qing, PhD
Phone
18650383162
Email
drmichaelzheng@qq.com
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
33598865
Citation
Zheng Q, Liu W, Huang Y, Gao Z, Wu Y, Wang X, Cai M, He Y, Chen S, Wang B, Liu L, Chen S, Huang H, Zheng L, Kang R, Zeng X, Chen J, Chen H, Chen J, Li Z, Shi G. Predictive Value of Active Sacroiliitis in MRI for Flare Among Chinese Patients with Axial Spondyloarthritis in Remission. Rheumatol Ther. 2021 Mar;8(1):411-424. doi: 10.1007/s40744-021-00279-y. Epub 2021 Feb 18.
Results Reference
derived
Learn more about this trial
Effects of Nonsteroidal Anti-Inflammatory Drugs in Recurrence of Spondyloarthritis Patients After Remission
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