UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000023989 |
|---|---|
| Receipt number | R000024831 |
| Scientific Title | Efficacy and safety of hydroxychloroquine for Japanese patients with rheumatoid arthritis |
| Date of disclosure of the study information | 2017/01/01 |
| Last modified on | 2023/09/02 05:16:11 |
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Basic information
Public title
Efficacy and safety of hydroxychloroquine for Japanese patients with rheumatoid arthritis
Acronym
Efficacy and safety of hydroxychloroquine for Japanese patients with rheumatoid arthritis
Scientific Title
Efficacy and safety of hydroxychloroquine for Japanese patients with rheumatoid arthritis
Scientific Title:Acronym
Efficacy and safety of hydroxychloroquine for Japanese patients with rheumatoid arthritis
Region
| Japan |
Condition
Condition
rheumatoid arthritis
Classification by specialty
| Clinical immunology |
Classification by malignancy
Others
Genomic information
NO
Objectives
Narrative objectives1
To evaluate the efficacy and safety in Japanese patients with rheumatoid arthritis
Basic objectives2
Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Confirmatory
Trial characteristics_2
Pragmatic
Developmental phase
Phase II,III
Assessment
Primary outcomes
Achievement rate of ACR20 at week 24
Key secondary outcomes
Achievement rate of improving DAS28 category at weeks 4, 8, 12 and 24
Achievement rate of low disease activity in DAS 28 at weeks 4, 8, 12 and 24
Achievement rate of clinical remission in DAS 28 at weeks 4, 8, 12 and 24
Achievement rate of functional remission in HAQ at weeks 4, 8, 12 and 24
Achievement rate of structural remission in modified total Sharp score at week 24
Achievement rate of ACR 20 at at weeks 4, 8, and 12
Achievement rate of ACR 50/70 at weeks 4, 8, 12 and 24
Adverse effects during whole study
Base
Study type
Interventional
Study design
Basic design
Single arm
Randomization
Non-randomized
Randomization unit
Blinding
Open -no one is blinded
Control
Historical
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment
Intervention
No. of arms
1
Purpose of intervention
Treatment
Type of intervention
| Medicine |
Interventions/Control_1
Treatment with hydroxyxhloroquine for 24 weeks.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10
Eligibility
Age-lower limit
| 18 | years-old | <= |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
Patients who fulfill the following four criteria in Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine
1) Age 18- years
2) RA satisfying either the 1987 ACR criteria or 2010 ACR/ EULAR criteria
3) active disease (DAS28 2.6-) with poor prognostic factors with methotrexate treatment for over 3 months (stable dose for at least 4 weeks) or active disease with two or more oral conventional synthetic DMARDs for over 3 months (stable dose for at least 4 weeks)
4) One or more swollen joints and one or more tender joints
5) Written informed consent provided
6) Prior use of biological agent is permitted
Key exclusion criteria
1) Pregnancy or hope to bear a child
2) Contraindication to HCQ, e.g. history of retinopathy and hypersensitivity to 4-aminoquinoline
3) Uncontrollable diabetes mellitus
4) Porphyria
5) Psoriasis
6) G6PD deficiency
7) Ineligible for the study judged by physicians
Target sample size
60
Research contact person
Name of lead principal investigator
| 1st name | Tsutomu |
| Middle name | |
| Last name | Takeuchi |
Organization
Keio University School of Medicine
Division name
Division of Rheumatology
Zip code
160-8582
Address
35 Shinanomachi, Shinjuku-ku, Tokyo, Japan
TEL
03-5363-3786
tsutake@z5.keio.jp
Public contact
Name of contact person
| 1st name | Yuko |
| Middle name | |
| Last name | Kaneko |
Organization
Keio University School of Medicine
Division name
Division of Rheumatology
Zip code
160-8582
Address
35 Shinanomachi, Shinjuku-ku, Tokyo, Japan
TEL
03-5363-3786
Homepage URL
ykaneko@z6.keio.jp
Sponsor or person
Institute
Division of Rheumatology, Keio University School of Medicine
Institute
Department
Personal name
Funding Source
Organization
Sanofi
Organization
Division
Category of Funding Organization
Profit organization
Nationality of Funding Organization
Other related organizations
Co-sponsor
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Certified Clinical Research Review Board, Keio University
Address
35 Shinanomachi, Shinjuku-ku, Tokyo, Japan
Tel
03-3353-1211
med-nintei-jimu@adst.keio.ac.jp
Secondary IDs
Secondary IDs
NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
Institutions
慶應義塾大学病院(東京都)
Other administrative information
Date of disclosure of the study information
| 2017 | Year | 01 | Month | 01 | Day |
Related information
URL releasing protocol
https://jrct.niph.go.jp/latest-detail/jRCTs031180050
Publication of results
Published
Result
URL related to results and publications
https://academic.oup.com/mr/advance-article-abstract/doi/10.1093/mr/roac153/6885349?redirectedFrom=f
Number of participants that the trial has enrolled
60
Results
The addition of HCQ to csDMARDs was effective, with no new safety signal in patients with RA.
Results date posted
| 2023 | Year | 09 | Month | 02 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Variables HCQ (n = 60)
Female 55 (91.7)
Age 63.7 (13.0)
Seropositive for RF or anti CCP 51 (85.0)
Disease duration, years 12.4 (10.4)
History of biological agent use 11 (18.3)
Methotrexate use 51 (85.0)
csDMARDs other than methotrexate 9 (15.0)
Concomitant glucocorticoid use 9 (15.0)
C reactive protein, mg per dL 0.7 (1.5)
Erythrocyte sedimentation rate, mm per hr 31.4 (26.4)
DAS28-ESR 4.4 (0.9)
DAS28-CRP 3.6 (0.8)
SDAI 17.9 (7.8)
CDAI 17.2 (7.4)
HAQ DI 0.7 (0.7)
DAS28-ESR low disease activity3 (5.0)
Swollen joint count 0-28 5.4 (3.3)
Tender joint count 0-28 4.6 (2.9)
Swollen joint count 0-66 7.0 (4.4)
Tender joint count 0-68 5.8 (4.0)
HAQ-DI remission 32 (53.3)
Patient global assessment, mm 32.4 (23.2)
Evaluator global assessment, mm 40.0 (22.8)
Pain visual analog scale, mm 32.3 (23.8)
HCQ dose
200 mg per day 24 (60.0)
200 mg and 400 mg on alternate days 34 (56.7)
400 mg per day 2 (3.3)
Participant flow
Sixty patients were enrolled and received HCQ. Seven patients withdrew during the 24-week period due to AEs (N = 6; skin rash in two patients, arthritis exacerbation in two patients, diarrhea in one patient, and tremor in one patient) and limited transportation to the hospital because of the Covid-19 pandemic (N = 1). Therefore, 53 patients completed HCQ therapy for 24 weeks and were considered candidates for propensity score matching.
As described in the Methods section, we identified 276 patients in our registry as candidates for propensity score matching for establishing a historical control group. By using propensity score matching, 46 patients in each group were selected for further analysis.
Adverse events
Fifty nine cases of Adverse events occurred in 36 patients . The most frequent adverse events were infections and infestations, which occurred in 15 patients, followed by gastrointestinal disorders in 11 patients. Although there were three events of bacterial pneumonia and one event of herpes zoster, they were treated without hospitalization and did not require HCQ cessation. Besides diarrhea, epigastralgia, stomatitis, loss of appetite, xerostomia and gingivitis were observed as non serious adverse events, all of which were cured with supportive treatment without reducing the dose of HCQ. Serious adverse events occurred in two patients (cataract operation with one-night hospitalization, and cerebral hemorrhage) during the 8 week post observation period. Six patients withdrew from the study before week 24 due to adverse events (one diarrhea, one tremor, two arthritis exacerbation, two drug-related eruptions). This Diarrhea and two drug-related eruptions which led to withdrawal occurred early after HCQ initiation (within 4 weeks). No HCQ retinopathy was observed during the study.
Outcome measures
Primary endpoint
Rate of achieving ACR20
Secondary endpoint
Achievement rate of improving more than one DAS28 category at week 4, week 8 and week 12
Achievement rate of low disease activity with DAS 28 at week 4, week8, week 12 and week 24
Achievement rate of clinical remission with DAS 28 at week 4, week8, week 12 and week 24
Achievement rate of functional remission with HAQ (HAQ less than 0.5) at week 4, week8, week 12 and week 24
Achievement rate of structural remission with modified total Sharp (TSS less than 0.5) score at week 4, week8, week 12 and week 24
Achievement rate of ACR20, 50, 70 at week 4, week8, week 12 and week 24
Rate of adverse effects during whole study
Exploratory endpoint
Serum cytokine levels at week 4, week8, week 12 and week 24
Peripheral blood cell surface markers at week 4, week8, week 12 and week 24
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Completed
Date of protocol fixation
| 2016 | Year | 08 | Month | 26 | Day |
Date of IRB
| 2015 | Year | 04 | Month | 14 | Day |
Anticipated trial start date
| 2016 | Year | 11 | Month | 01 | Day |
Last follow-up date
| 2019 | Year | 06 | Month | 30 | Day |
Date of closure to data entry
| 2019 | Year | 09 | Month | 30 | Day |
Date trial data considered complete
| 2019 | Year | 10 | Month | 30 | Day |
Date analysis concluded
| 2020 | Year | 04 | Month | 01 | Day |
Other
Other related information
Management information
Registered date
| 2016 | Year | 09 | Month | 09 | Day |
Last modified on
| 2023 | Year | 09 | Month | 02 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024831
