46. Malignant rheumatoid arthritis Clinical trials / Disease details
Clinical trials : 4,356 / Drugs : 2,567 - (DrugBank : 415) / Drug target genes : 192 - Drug target pathways : 228
| No. | TrialID | Date_ enrollment | Date_ registration | Public_title | Scientific_title | Condition | Intervention | Primary_ sponsor | Secondary_ sponsor | Recruitment_ Status | Inclusion_ agemin | Inclusion_ agemax | Inclusion_ gender | Target_ size | Phase | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | ITMCTR2200006853 | 2022-12-14 | 2022-12-06 | Clinical study on the treatment of advanced rheumatoid arthritis (Phlegm stasis bi syndrome) by Soufeng Sanjie fomula for inhibiting bone erosion | medicine | Rheumatoid arthritis | control group:MTX;Observation group:MTX+Traditional Chinese medicine (TCM); | Jiangsu Integrated Traditional Chinese and Western Medicine Hospital | NULL | Recruiting | 18 | 70 | Both | control group:30;Observation group:30; | China | |
| 2 | ITMCTR2100005379 | 2021-12-01 | 2021-12-06 | Clinical Study on Treatment of Damp Heat Stagnation Syndrome of Rheumatoid Arthritis by SiMiaoXiaoLing Zhiwang Prescription | Clinical Study on Treatment of Damp Heat Stagnation Syndrome of Rheumatoid Arthritis by SiMiaoXiaoLing Zhiwang Prescription | Rheumatism | The treatment group:Simiaoxiaoling Zhiwang Decoction (granule) + methotrexate + folic acid tablets;The control group:methotrexate + folic acid tablets; | Yunnan Hospital of Traditional Chinese Medicine | NULL | Recruiting | 18 | 70 | Both | The treatment group:36;The control group:36; | China | |
| 3 | ITMCTR2100005057 | 2021-09-29 | 2021-07-16 | Prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial of Qufengzhitong capsule in the treatment of rheumatoid arthritis | Prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial of Qufengzhitong capsule in the treatment of rheumatoid arthritis | rheumatoid arthritis | control group:Methotrexate tablets+Qufeng Zhitong Capsule Placebo;Test group:Methotrexate tablets+Qufengzhitong capsule; | Guang'anmen Hospital, China Academy of Chinese Medical Sciences | NULL | Pending | 18 | 75 | Both | control group:102;Test group:102; | Phase 4 | china |
| 4 | ITMCTR2100005066 | 2021-07-15 | 2021-07-16 | A prospective non-randomized controlled study on the treatment of interstitial pneumonia of RA with Peitushengjinjiedutongluo method | A prospective cohort study on the treatment of interstitial pneumonia of RA with Peitushengjinjiedutongluo method | Rheumatoid arthritis with interstitial pneumonia | control group:Hydroxychloroquine + prednisone;experimental group:Syndrome Differentiation and Flavoring of Peitushengjin Chinese Medicine Granules; | Zhejiang Chinese Medical University | NULL | Pending | 18 | 65 | Both | control group:240;experimental group:285; | N/A | China |
| 5 | ITMCTR2100004848 | 2021-05-15 | 2021-05-15 | Clinical study on the therapeutic effect of Juanbi Qianggu Formula combined with DMARDs on Rheumatoid Arthritis with liver and kidney deficiency | Clinical study on the therapeutic effect of Juanbi Qianggu Formula combined with DMARDs on Rheumatoid Arthritis with liver and kidney deficiency | rheumatoid arthritis | Control group:Methotrexate 10mg qw;Experimental group:Methotrexate 10mg qw+ Juanbiqianggu prescription 1 bag of tid; | Shanghai Guanghua Integrated traditional Chinese and Western Medicine Hospital | NULL | Recruiting | Both | Control group:40;Experimental group:40; | China | |||
| 6 | ITMCTR2100004321 | 2021-01-25 | 2021-01-25 | Observation on the clinical effect of treating rheumatoid arthritis based on the theory of kidney deficiency and cold coagulation | Observation on the clinical effect of treating rheumatoid arthritis based on the theory of kidney deficiency and cold coagulation | Rheumatoid Arthritis | control group:Methotrexate tablets + Folic acid tablets;experimental group:Fuzi Guizhi Decoction granules+Methotrexate tablets + Folic acid tablets; | The Affiliated Hospital of Yunnan University of Traditional Chinese Medicine | NULL | Recruiting | 18 | 65 | Both | control group:36;experimental group:36; | China | |
| 7 | ITMCTR2100004302 | 2021-01-21 | 2021-01-21 | Observation on Qingre Tongluo recipe in the treatment of difficult-to-treat rheumatoid arthritis with heat syndrome and its effect on drug resistance gene | Observation on Qingre Tongluo recipe in the treatment of difficult-to-treat rheumatoid arthritis with heat syndrome and its effect on drug resistance gene | difficult-to-treat rheumatoid arthritis | The normal group:No special treatment;Refractory (control group):Methotrexate + folic acid tablets + adalimumab + simulant;Refractory (trial group):Methotrexate + folic acid tablets + Adalimumab + Qingre Tongluo Prescription; Primary untreated group:Do not give any treatment, only before treatment for blood, the group does not consider follow-up treatment, recommended patients to seek medical advice, follow the doctor 's orders;Therapeutic effective group:Continue the original treatment plan; | Yunnan Hospital of Traditional Chinese Medicine/The First Affiliated Hospital of Yunnan University of traditional Chinese Medicine | NULL | Recruiting | 18 | 70 | Both | The normal group:15;Refractory (control group):15;Refractory (trial group):15; Primary untreated group:15;Therapeutic effective group:15; | China | |
| 8 | ChiCTR2100042440 | 2021-01-21 | 2021-01-21 | Observation on Qingre Tongluo recipe in the treatment of difficult-to-treat rheumatoid arthritis with heat syndrome and its effect on drug resistance gene | Observation on Qingre Tongluo recipe in the treatment of difficult-to-treat rheumatoid arthritis with heat syndrome and its effect on drug resistance gene | difficult-to-treat rheumatoid arthritis | The normal group:No special treatment; Primary untreated group:Do not give any treatment, only before treatment for blood, the group does not consider follow-up treatment, recommended patients to seek medical advice, follow the doctor 's orders;Therapeutic effective group:Continue the original treatment plan;Refractory (trial group):Methotrexate + folic acid tablets + Adalimumab + Qingre Tongluo Prescription;Refractory (control group):Methotrexate + folic acid tablets + adalimumab + simulant; | Yunnan Hospital of Traditional Chinese Medicine/The First Affiliated Hospital of Yunnan University of traditional Chinese Medicine | NULL | Recruiting | 18 | 70 | Both | The normal group:15; Primary untreated group:15;Therapeutic effective group:15;Refractory (trial group):15;Refractory (control group):15; | China | |
| 9 | ITMCTR2100004288 | 2021-01-19 | 2021-01-19 | Effect of Wenyang Tongluo Recipe on Cold Syndrome of Rheumatoid Arthritis and Drug Resistant Gene | Effect of Wenyang Tongluo Recipe on Cold Syndrome of Rheumatoid Arthritis and Drug Resistant Gene | Rheumatoid arthritis | Observation group:Methotrexate + folic acid tablets + Adamumab + Wenyang Tongluo Recipient;Primary untreated group:No treatment was given, only blood was drawn before treatment, and follow-up treatment was not considered in this group. Patients were advised to seek medical treatment by themselves and follow the doctor's advice;Therapeutic effective group:Continue with the original regimen;The control group:Methotrexate + folic acid tablets + adamulizumab + simulation agent;The normal group:No special treatment will be given; | Yunnan Hospital of Traditional Chinese Medicine (The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine) | NULL | Recruiting | 18 | 70 | Both | Observation group:15;Primary untreated group:15;Therapeutic effective group:15;The control group:15;The normal group:15; | China | |
| 10 | ChiCTR2100042328 | 2021-01-19 | 2021-01-19 | Effect of Wenyang Tongluo Recipe on Cold Syndrome of Rheumatoid Arthritis and Drug Resistant Gene | Effect of Wenyang Tongluo Recipe on Cold Syndrome of Rheumatoid Arthritis and Drug Resistant Gene | Rheumatoid arthritis | The normal group:No special treatment will be given;Primary untreated group:No treatment was given, only blood was drawn before treatment, and follow-up treatment was not considered in this group. Patients were advised to seek medical treatment by themselves and follow the doctor's advice;Therapeutic effective group:Continue with the original regimen;Observation group:Methotrexate + folic acid tablets + Adamumab + Wenyang Tongluo Recipient;The control group:Methotrexate + folic acid tablets + adamulizumab + simulation agent; | Yunnan Hospital of Traditional Chinese Medicine (The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine) | NULL | Recruiting | 18 | 70 | Both | The normal group:15;Primary untreated group:15;Therapeutic effective group:15;Observation group:15;The control group:15; | China | |
| 11 | ITMCTR2100004239 | 2021-01-01 | 2021-01-09 | Clinical study on Yupingfengguizhi solution assisted hormone Withdrawal and reduction in rheumatoid arthritis (Wind-Cold-Dampness Arthralgia Syndrome) | Clinical study on Yupingfengguizhi solution assisted hormone Withdrawal and reduction in rheumatoid arthritis (Wind-Cold-Dampness Arthralgia Syndrome) | Rheumatoid arthritis | control group:Prednisone Acetate Tablets, Methotrexate, Leflunomide;Treatment group:Yupingfengguizhi solution, Prednisone Acetate Tablets, Methotrexate, Leflunomide ; | Yunnan Traditional Chinese Medicine Hospital | NULL | Recruiting | 18 | 65 | Both | control group:31;Treatment group:62; | China | |
| 12 | ITMCTR2100004610 | 2021-01-01 | 2021-01-05 | Clinical study on Juanbi granule in adjuvant hormone withdrawal of rheumatoid arthritis | Clinical study on Juanbi granule in adjuvant hormone withdrawal of rheumatoid arthritis | rheumatoid arthritis | control group:Prednisone Acetate Tablets, Methotrexate and Leflunomide;Treatment group:Juanbi granule, Prednisone Acetate Tablets, Methotrexate and Leflunomide ; | Yunnan Hospital of Traditional Chinese Medicine /The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine | NULL | Recruiting | 18 | 65 | Both | control group:31;Treatment group:62; | China | |
| 13 | ITMCTR2000003610 | 2021-01-01 | 2020-08-21 | A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Duhuo Jisheng Tang in The Treatment of Rheumatoid Arthritis by Regulating Lymphatic Drainage | A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Duhuo Jisheng Tang in The Treatment of Rheumatoid Arthritis by Regulating Lymphatic Drainage | Rheumatoid Arthritis | Control group:Duhuo Jisheng Tang placebo, MTX as base treatment.;Experimental group:Duhuo Jisheng Tang, MTX as base treatment.; | Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine | NULL | Pending | 18 | 70 | Both | Control group:60;Experimental group:60; | China | |
| 14 | ITMCTR2100004638 | 2021-01-01 | 2021-01-06 | Observation on the clinical curative effect of external application of Rebi ointment in treating rheumatoid arthritis (damp-heat syndrome) joint pain | Observation on the clinical curative effect of external application of Rebi ointment in treating rheumatoid arthritis (damp-heat syndrome) joint pain | Rheumatoid Arthritis | Control group:Rebi cream simulant, Methotrexate tablets, Leflunomide tablets, and Folic acid tablets;therapy group:Rebi ointment, Methotrexate tablets, Leflunomide tablets, and Folic acid tablets ; | Yunnan Provincial Hospital of Traditional Chinese Medicine/The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine | NULL | Recruiting | 18 | 70 | Both | Control group:36;therapy group:36; | China | |
| 15 | ChiCTR2000037675 | 2020-10-01 | 2020-08-30 | Clinical study of Shenshi Qianghuo Dihuang Decoction in the treatment of Rheumatoid arthritis from the perspective of ''7+1'' | Clinical study of Shenshi Qianghuo Dihuang Decoction in the treatment of Rheumatoid arthritis from the perspective of ''7+1'' | Rheumatoid arthritis | control group:Methotrexate;experimental group:Qianghuo Dihuang Decoction + Methotrexate; | Shanghai Traditional Chinese Medicine Hospital | NULL | Recruiting | Both | control group:72;experimental group:72; | China | |||
| 16 | ChiCTR2000035146 | 2020-08-01 | 2020-08-02 | The effect of the IPACK block on pain after primary TKA in different levels of knee flexion deformity patients: a prospective, cohort trial | The effect of the IPACK block on pain after primary TKA in different levels of knee flexion deformity patients: a prospective, cohort trial | knee osteoarthritis/ knee rheumatoid arthritis | The knee flexion deformities of different degrees were divided into different groups, and the patients without knee flexion deformity were the control group:Under the guidance of ultrasound, 20 ml 0.25% ropivacaine was injected between popliteal artery and knee joint capsule; | West China Hospital, Sichuan University | NULL | Pending | 18 | 80 | Both | The knee flexion deformities of different degrees were divided into different groups, and the patients without knee flexion deformity were the control group:80; | N/A | China |
| 17 | ITMCTR1900002628 | 2020-04-01 | 2019-09-28 | A prospective, multicenter, randomized, open study on the efficacy and safety of Yisaipu combined with traditional Chinese medicine for standard treatment and maintenance therapy in RA patients who failed traditional DMARDs treatment | A prospective, multicenter, randomized, open study on the efficacy and safety of Yisaipu combined with traditional Chinese medicine for standard treatment and maintenance therapy in RA patients who failed traditional DMARDs treatment | Rheumatoid arthritis | the experimental group:Subcutaneously injected 50mg per week for 24 weeks. From 24 weeks to 52 weeks, Yisaipu and TCM were maintained;the control group 1:Subcutaneously injected 50mg per week for 24 weeks. From 24 weeks to 52 weeks, Yisaipu dosage reduction combined with traditional Chinese medicine was maintained;the control group 2:Subcutaneously injected 50mg per week for 24 weeks.From 24 weeks to 52 weeks, TCM maintenance treatment; | Guang'anmen Hospital, China Academy of Chinese Medical Sciences | NULL | Pending | 18 | 65 | Both | the experimental group:40;the control group 1:30;the control group 2:30; | Phase 4 | China |
| 18 | ChiCTR1900026270 | 2020-04-01 | 2019-09-28 | A prospective, multicenter, randomized, open study on the efficacy and safety of Yisaipu combined with traditional Chinese medicine for standard treatment and maintenance therapy in RA patients who failed traditional DMARDs treatment | A prospective, multicenter, randomized, open study on the efficacy and safety of Yisaipu combined with traditional Chinese medicine for standard treatment and maintenance therapy in RA patients who failed traditional DMARDs treatment | Rheumatoid arthritis | the experimental group:Subcutaneously injected 50mg per week for 24 weeks. From 24 weeks to 52 weeks, Yisaipu and TCM were maintained;the control group 1:Subcutaneously injected 50mg per week for 24 weeks. From 24 weeks to 52 weeks, Yisaipu dosage reduction combined with traditional Chinese medicine was maintained;the control group 2:Subcutaneously injected 50mg per week for 24 weeks.From 24 weeks to 52 weeks, TCM maintenance treatment; | Guang'anmen Hospital, China Academy of Chinese Medical Sciences | NULL | Pending | 18 | 65 | Both | the experimental group:40;the control group 1:30;the control group 2:30; | Phase 4 | China |
| 19 | ITMCTR1900002503 | 2019-08-01 | 2019-08-03 | A randomized, double-blind, prospective, controlled trial for Yishen-Tongbi-Tang in the treatment of active rheumatoid arthritis | A randomized, double-blind, prospective, controlled trial for Yishen-Tongbi-Tang in the treatment of active rheumatoid arthritis | Rheumatoid Arthritis | Positive control group:Methotrexate;Experimental group:Traditional Chinese medicine (Yi-Shen Tong-Bi Tang); | The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine | NULL | Pending | 18 | 65 | Both | Positive control group:50;Experimental group:50; | N/A | China |
| 20 | ChiCTR1900024902 | 2019-08-01 | 2019-08-03 | A randomized, double-blind, prospective, controlled trial for Yishen-Tongbi-Tang in the treatment of active rheumatoid arthritis | A randomized, double-blind, prospective, controlled trial for Yishen-Tongbi-Tang in the treatment of active rheumatoid arthritis | Rheumatoid Arthritis | Experimental group:Traditional Chinese medicine (Yi-Shen Tong-Bi Tang);Positive control group:Methotrexate; | The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine | NULL | Pending | 18 | 65 | Both | Experimental group:50;Positive control group:50; | N/A | China |
| 21 | ChiCTR1800019277 | 2018-11-01 | 2018-11-02 | The Zoledronic Acidameliorate theSecondary Osteoporosis in Rheumatoid Arthritis patients | The Zoledronic Acidameliorate theSecondary Osteoporosis in Rheumatoid Arthritis patients | Rheumatoid Arthritis | Control group:MTX;Treatment group 1:Zoledronate Acid(ZA);Treatment group 2:MTX+Zoledronate Acid; | Shanghai Traditional Medicine University Affiliated Guanghua Hospital | NULL | Recruiting | 18 | 65 | Both | Control group:22;Treatment group 1:22;Treatment group 2:22; | China | |
| 22 | EUCTR2017-004226-15-DK (EUCTR) | 26/10/2018 | 05/01/2018 | Can-Art Effect and safety of using Canabis derivatives for the treatment of pain in patients with inflammatory Arthritis, such as reumatoid arthritis and ankylosing spondylitis, the latter being a type of arthritis that causes a long term inflammation of the joints of the spine. A randomized, double blinded, placebo controlled trial, i.e. in this drug trial, a control group is given a placebo while another group is given the Cannabis derivative being studied. | CAN-ART The efficacy and safety of using cannabis derivatives cannabidiol (CBD) and tetrahydrocannabinol (THC) for the treatment of pain in patients with inflammatory arthritis (RA, AS). A randomized, double blinded, placebo controlled trial - Can-Art | Rheumatoid Arthritis (RA) and Ankylosing Spondylitis (AS) MedDRA version: 20.0;Level: PT;Classification code 10039073;Term: Rheumatoid arthritis;System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders MedDRA version: 20.0;Classification code 10002556;Term: Ankylosing spondylitis;System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders ;Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05] | Product Name: Cannabidiol tablet 10 mg Other descriptive name: CANNABIDIOL Product Name: Dronabinol capsule 2.5. mg INN or Proposed INN: DRONABINOL | King Christian 10th Hospital for Rheumatology | NULL | Not Recruiting | Female: yes Male: yes | 180 | Human pharmacology (Phase 1): no Therapeutic exploratory (Phase 2): yes Therapeutic confirmatory - (Phase 3): no Therapeutic use (Phase 4): no | Denmark | ||
| 23 | ChiCTR-IPR-16009029 | 2016-11-01 | 2016-08-15 | Clinical Study of the Bone Protection Effect of Biqi Capsule for Treatment of Rheumatoid Arthritis | Clinical Study of the Bone Protection Effect of Biqi Capsule for Treatment of Rheumatoid Arthritis | Rheumatoid arthritis | RA:the experimental group:MTX 10-15mg po qw+BiQi Capsule, 1.2g po bid;RA:the control group:MTX 10-15mg po qw+LEF, 10mg, po, bid;OA:The traditional Chinese group:BiQi Capsule, 1.2g po bid+Celecoxib capsules 0.2g po take as needed;OA:The western medicine control group:Calcitriol Soft Capsules 0.25ug, po, bid+Celecoxib capsules 0.2g po take as needed; | Guangdong Provincial Hospital of Chinese Medicine | NULL | Pending | 18 | 65 | Both | RA:the experimental group:60;RA:the control group:60;OA:The traditional Chinese group:60;OA:The western medicine control group:60; | China | |
| 24 | ChiCTR-IPR-16008793 | 2016-07-15 | 2016-06-10 | A multi center, randomized, double blind, positive parallel controlled clinical study of Zhengqing Fengtongning sustained release tablets in the treatment of rheumatoid arthritis | A multi center, randomized, double blind, positive parallel controlled clinical study of Zhengqing Fengtongning sustained release tablets in the treatment of rheumatoid arthritis | Rheumatoid arthritis | experimental group:ZHENGQING FENGTONGNING sustained release tablets; control group:methotrexate;The combined treatment group:ZHENGQING FENGTONGNING sustained release tablets combine methotrexate; | The First Affiliated Hospital of Third Military Medical University | NULL | Recruiting | 18 | 75 | Both | experimental group:80; control group:80;The combined treatment group:80; | China | |
| 25 | ChiCTR1800019290 | 2014-01-01 | 2018-11-03 | The Zoledronic Acidameliorate theSecondary Osteoporosis in Rheumatoid Arthritis patients | The Zoledronic Acidameliorate theSecondary Osteoporosis in Rheumatoid Arthritis patients | Rheumatoid Arthritis | Control group:MTX;Treatment group 1:ZA;Treatment group 2:MTX+ZA; | Xiao Lianbo | NULL | Completed | 18 | 65 | Both | Control group:22;Treatment group 1:22;Treatment group 2:22; | 2 (Phase 2 study) | China |
| 26 | JPRN-UMIN000006702 | 2012/02/01 | 11/11/2011 | A parallel group, randomized clinical trial on the efficacy and safety of intensive treatment strategy with MTX as the anchor-drug in patients with active early rheumatoid Arthritis | A parallel group, randomized clinical trial on the efficacy and safety of intensive treatment strategy with MTX as the anchor-drug in patients with active early rheumatoid Arthritis - An intensive treatment strategy in patients with active early RA | rheumatoid arthritis | Intensive treatment group Period: 24 weeks In the intensive treatment group, a patient starts treatment with MTX at 8mg/week. Dosage is increased to 0.25mg/kg/week by week 8 and is further increased to his or her maximum tolerable dosage by week 12. The maximum tolerable dosage is maintained until week 24. If a patient shows inadequate response to MTX and does not achieve SDAI(simplified disease activity index)emission or CDAI (linical disease activity index)remission by week 16, additional treatment with tacrolimus, bucillamine, sarazosulfapyridine, or biologics will be started as scheduled in the protocol. After week 24, both groups receive treatments by attending rheumatologists'discretion and are followed until week 72. Conventional treatment group Period: 24 weeks In the control group, a patient starts treatment with MTX, tacrolimus, bucillamine, sarazosulfapyridine, or biologics by attending rheumatologists' discretion by week 24. Biologics are allowed on and after week 12. After week 24, both groups receive treatments by attending rheumatologists'discretion and are followed until week 72. | Tokyo Medical and Dental University | Department of Pharmacovigilance | Complete: follow-up continuing | 20years-old | 70years-old | Male and Female | 290 | Not applicable | Japan |
| 27 | NCT02779114 (ClinicalTrials.gov) | January 2009 | 16/5/2016 | RETRO (REduction of Therapy in RA Patients in Ongoing Remission) | A Phase 3, Multicenter, Randomized, Open, Prospective, Controlled, Parallel Group Study of Reduction of Therapy in Patients With Rheumatoid Arthritis in Ongoing Remission. | Rheumatoid Arthritis | Drug: Control group;Other: Reduction group 1;Other: Reduction group 2 | University of Erlangen-Nürnberg Medical School | NULL | Recruiting | 18 Years | N/A | Both | 318 | Phase 3 | Germany |
| 28 | ChiCTR-TRC-10000850 | 2008-10-01 | 2010-04-26 | Phase III clinical trial of Iguratimodin rheumatoid arthritis | Phase III clinical trial of Iguratimodin rheumatoid arthritis | rheumatoid arthritis | 3:Experimental group: Iguratimod tablet, nimesulide dummy tablet; positive control group: taking nimesulide and Iguratimod dummy tablet; placebo group: taking Iguratimod dummy tablet and nimesulide dummy tablet. ; | Anhui Medical University | NULL | Completed | 18 | 65 | Both | 3:600; | 3 (Phase 3 study) | China |