慢性阻塞性肺病患者激素撤退试验

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试验详情

一、临床试验项目名称
慢性阻塞性肺病患者激素撤退试验

二、适应症
慢性阻塞性肺病

三、试验介绍

澄清接受优化疗法（根据指导原则）的重度极重度COPD患者持续使用iCS的必要性，考察iCS逐步撤退对这部分患者的影响。了解患者人群的特征，分析患者表型和基因型，鉴定亚组人群和激素适用标志物。

研究中心所在省份及城市（具体启动情况以后期咨询为准）

研究中心	主要研究者
广州医学院第一附属医院	钟南山

序号	机构名称	主要研究者	国家	省（州）	城市
1	广州医学院第一附属医院	钟南山	中国	广东	广州
2	北京医科大学第三医院	姚婉贞	中国	北京	北京
3	首都医科大学附属北京朝阳医院	林英翔	中国	北京	北京
4	复旦大学中山医院	白春学	中国	上海	上海
5	上海肺科医院	李惠萍	中国	上海	上海
6	北京协和医院	蔡柏蔷	中国	北京	北京
7	华中科技大学同济医学附属协和医院	辛建保	中国	湖北	武汉
8	重庆医科大学附属第一医院	吴亚梅	中国	重庆	重庆
9	广州医学院第一附属医院	汤彦	中国	广东	广州
10	Westmead Hospital	John Wheatley	Australia	NSW	Westmead
11	The Burnside War Memorial Hospital	Michael Chia	Australia	SA	Toorak Gardens
12	Repatriation General Hospital	Dimitar Sajkov	Australia	SA	Daw Park
13	The Queen Elizabeth Hospital	Jonathan Polasek	Australia	SA	Woodville
14	Concord Repatriation General Hospital	Matthew Peters	Australia	NSW	Concord
15	P3 Research	Dean Quinn	New Zealand	N/A	Newtown Wellington NZ
16	P3 Research	Eunice Kelly	New Zealand	N/A	Tauranga
17	Christchurch Hospital	Michael Epton	New Zealand	N/A	Christchurch
18	Dunedin Hospital	Benedict Brockway	New Zealand	N/A	Dunedin
19	Middlemore Hospital	Stuart Jones	New Zealand	N/A	Otahuhu New Zealand
20	Waikato Hospital	Graham Mills	New Zealand	N/A	Hamilton
21	University of Auckland	Tanya McWilliams	New Zealand	N/A	Auckland NZ
22	U.Z. Gasthuisberg	Marc Decramer	Belgium	N/A	Leuven
23	CHU St. Pierre	Vincent Ninane	Belgium	N/A	Bruxelles
24	A.Z. Middelheim	Lieven Bedert	Belgium	N/A	Middelheim
25	Clinique et maternite Sainte-Elisabeth	Jean-Benoit Martinot	Belgium	N/A	Namur
26	Prive Praktijk	Luc Van Zandweghe	Belgium	N/A	Lebbeke
27	CHU de Charleroi - Hopital Andre Vesale	Rudi Peche	Belgium	N/A	Montigny-le-Tilleul
28	AZ Turnhout	Peter Driesen	Belgium	N/A	Turnhout
29	AZ St.-Elisabeth	Yves Mentens	Belgium	N/A	Herentals
30	Hospital St Nicolas	Bernard Plas	Belgium	N/A	Eupen
31	Clinique Parc Leopold	Alfred Flemale	Belgium	N/A	Bruxelles
32	Hospital Saint Joseph	Pierre Fievez	Belgium	N/A	Gilly
33	Hospital Saeo Lucas da PUC do Rio Grande do Sul	Carlos Fritscher	Brazil	RS	Porto Alegre
34	Hospital Geral de Goiania	Heicilainy Gondim	Brazil	GO	Goiania
35	Lar Escola Saeo Francisco	Jose Roberto Brito Jardim	Brazil	SP	Sao Paulo
36	Hospital das Clinicas da Universidade Federal de Goias	Maria Auxiliadora Carmo Moreira	Brazil	GO	Goiania
37	Irmandade Santa Casa de Misericordia de Porto Alegre	Rubin Adalberto	Brazil	RS	Porto Alegre
38	Tri-service General Hospital	Wann-Cherng Perng	中国	N/A	Taipei
39	National Taiwan University Hospital	Ping-Hung Kuo	中国	N/A	Taipei
40	Cheng Ching General Hospital-Chung Kang Branch	Ren-Guang Wu	中国	N/A	Taichung
41	Kaohsiung Medical University Chung-Ho Memorial Hospital	Ming-Shyan Huang	中国	N/A	Kaohsiung
42	Chung Shan Medical University Hospital	Chang-Yao Tsao	中国	N/A	Taiwan
43	China Medical University Hospital	Liang-Wen Hang	中国	N/A	Taiwan
44	MCU-Filemon Dionisio Tanchoco Medical Foundation	Lalaine Mortera	Philippines	N/A	Caloocan
45	Philippine General Hospital	Camilo Roa	Philippines	N/A	Manila
46	Manila Doctors Hospital	Aileen Wang	Philippines	N/A	Manila
47	Philippine Heart Center	Teresita De Guia	Philippines	N/A	Quezon
48	National Kidney & Transplant Institute	Manuel Jorge	Philippines	N/A	Quezon
49	FEU-NRMF Medical Center	Val Custodio	Philippines	N/A	Quezon
50	Quirino Memorial Medical Center	Joel Santiaguel	Philippines	N/A	Quezon
51	Asian Hospital & Medical Center	Lenora Fernandez	Philippines	N/A	Muntinlupa
52	Aarhus Sygehus	Ronald Dahl	Denmark	N/A	Aarhus C
53	Odense Universitetshospital	Ingrid Titlestad	Denmark	N/A	Odense C
54	Bispebjerg Hospital	Vibeke Backer	Denmark	N/A	Kobenhavn NV
55	Pneumologisches Forschungsinstitut GmbH	Helgo Magnussen	Germany	N/A	Grosshansdorf
56	Klinik Donaustauf	Michael Pfeifer	Germany	N/A	Donaustauf
57	Universitatsklinikum Koeln	Andrea Koch	Germany	N/A	Koeln
58	Universitatsklinikum Mainz	Stephanie Korn	Germany	N/A	Mainz
59	Universitatsklinikum Gieben und Marburg	Claus Vogelmeier	Germany	D	Marburg
60	Universitatsklinikum Heidelberg	Felix Herth	Germany	N/A	Heidelberg
61	Klinik fur Pneumologie, Allergologie und Schlafmedizin	Juliane Kronsbein	Germany	N/A	Bochum
62	Klinische Forschung Berlin Mitte	Ruth Knorr	Germany	N/A	Berlin
63	IKF Pneumologie GmbH & Co.KG	Andreas Eich	Germany	N/A	Frankfurt
64	Lungenfachklinik Immenhausen	Stefan Andreas	Germany	N/A	Immenhausen
65	Medizinische Klinik und Poliklinik I	Claus Neurohr	Germany	N/A	Munchen
66	Klinik fur Allgemeine Innere Medizin	Burkhard Bewig	Germany	N/A	Kiel
67	MECS GmbH	Frank Kaessner	Germany	N/A	Cottbus
68	Atemwegszentrum Neukolln	Rainer Gebhardt	Germany	N/A	Berlin
69	MECS Mommsenstr. 2 a GmbH	Ralf Schultebraucks	Germany	N/A	Berlin
70	Facharztzentrum am Krankenhaus	Winfried Schroeder-Babo	Germany	N/A	Gelnhausen
71	Lungenpraxis am Maingau	Peter Kardos	Germany	N/A	Frankfurt/Main
72	Pneumologisches Forschungsinstitut GmbH	Petra Mikloweit	Germany	N/A	Geesthacht
73	Praxis Dr. Keller	Claus Keller	Germany	N/A	Frankfurt
74	Hospital del Mar	Antonio Ferrer	Spain	N/A	Barcelona
75	Hospital de Cruces	Juan Bautista Galdiz Iturri	Spain	Spain	Barakaldo (Bilbao)
76	Hospital Clinic i Provincial de Barcelona	Roberto Rodriguez - Roisin	Spain	Spain	Barcelona
77	Hospital Son Espases (Antes Son Dureta)	Alberto Alonso	Spain	Spain	Palma de Mallorca
78	Complejo Hospitalario Infanta Cristina	Jose Antonio Gutierrez Lara	Spain	Spain	Badajoz
79	Ciutat Sanitaria Universitaria de Bellvitge	Eva Farrero	Spain	Spain	Hospitalet de Llobregat
80	Clinica Quiron Madrid	Jose Maria Echave Sustaeta	Spain	N/A	Pozuelo de Alarcon
81	Hospital Universitario Virgen del Rocio	Pilar Cejudo	Spain	Spain	Sevilla
82	Hospital Santa Catarina	Juan Roldan	Spain	N/A	Salt
83	Hospital Nord	Pascal Chanez	France	N/A	Marseille
84	CH Sud Reunion	Fabrice Paganin	France	N/A	Saint-Pierre
85	CH Sud Reunion	Claude Arvin-Berod	France	N/A	Saint-Pierre
86	Groupe Hospitalier Sud Reunion	Eric Huchot	France	N/A	Saint Pierre
87	Hospital sud de la Reunion	Vincent Boulay	France	N/A	Saint Pierre la Reunion
88	Centre Hospitalier Sainte Barbe - Unisante	Martine Claussner Paulignan	France	N/A	Forbach
89	Hospital de la Cavale Blanche	Christophe Gut Gobert	France	N/A	Brest
90	Hospital de la Cavale Blanche	Christophe Leroyer	France	N/A	Brest
91	Hospital de la Cavale Blanche	Francis Couturaud	France	N/A	Brest
92	Clinique du Parc	Philippe Tarodo de la Fuente	France	N/A	Castelnau le Lez
93	Clinique du Parc	Christophe Brousse	France	N/A	Castelnau le Lez
94	Clinique du Parc	Olivier Ortega	France	N/A	Castelnau le Lez
95	Cabinet Medical	Jacques Dupouy	France	N/A	Nimes
96	Hospital Laennec	Antoine Magnan	France	N/A	Nantes
97	Hospital Laennec	Patrick Germaud	France	N/A	Nantes
98	Hospital Laennec	Arnaud Cavailles	France	N/A	Nantes
99	Hospital Arnaud de Villeneuve	Lahouari Meziane	France	N/A	Montpellier
100	Hospital Arnaud de Villeneuve	Xavier Quantin	France	N/A	Montpellier
101	Institut Arnault Tzanck	Olivier Castelnau	France	F	Saint Laurent du Var
102	Institut Arnault Tzanck	Guy Rene Boyer	France	F	Saint Laurent du Var
103	Cabinet Medical	Serge Verdier	France	N/A	Perpignan
104	Cabinet Medical	Michel Hernandez	France	N/A	Perpignan
105	Cabinet Medical	Monique Verdier	France	N/A	Perpignan
106	Hospital Caremeau	Charles Le Merre	France	N/A	Nimes
107	Hospital Caremeau	Alain Proust	France	N/A	Nimes
108	Hospital Caremeau	Patrice Ray	France	N/A	Nimes
109	Hospital Europeen Marseille	Herve Pegliasco	France	F	Marseille
110	Centre Medical Erdre Saint Augustin	Jean-Yves Jasnot	France	N/A	Nantes
111	Hospital Gabriel Montpied	Denis Caillaud	France	N/A	Clermont Ferrand
112	Hospital Larrey	Roger Escamilla	France	F	Toulouse
113	Hospital Larrey	Danielle Brouquieres	France	F	Toulouse
114	Hospital Larrey	Marie-Christine Pujazon	France	F	Toulouse
115	Clinique Pasteur	Christophe Raspaud	France	N/A	Toulouse
116	Hospital Abderrahmen Mami	Abdelattif Chabbou	Tunisia	N/A	Ariana
117	Hospital Abderrahmen Mami	Mohamed Lamine Megdiche	Tunisia	N/A	Ariana
118	Hospital Charles Nicolle	Hend Bouacha	Tunisia	N/A	Tunis
119	CHU Farhet Hached	Mohamed Benzarti	Tunisia	N/A	Sousse
120	CHU Hedi Chaker	Abdelkader Ayoub	Tunisia	N/A	Sfax
121	General Hospital of Thessaloniki	Lazaros Sichletides	Greece	N/A	Thessaloniki
122	General Hospital of Thessaloniki	Marianna Kakoura	Greece	N/A	Thessaloniki
123	Athens Hospital of Chest Diseases	Panagiotis Demertzis	Greece	N/A	Athens
124	Athens Hospital of Chest Diseases	Nikolaos Koulouris	Greece	N/A	Athens
125	Sotiria General Hospital of Chest Diseases of Athens	Michail Toubis	Greece	N/A	Athens
126	University Hospital of Heraklion	Nicolaos Siafakas	Greece	N/A	Heraklion
127	Attikon, Panepistimiako Geniko Nosokomeio	Spyros Papiris	Greece	N/A	Athens
128	Evangelismos Hospital	Theodoros Vassilakopoulos	Greece	N/A	Athens
129	University Hospital of Larisa	Konstantinos Gourgoulianis	Greece	N/A	Larisa
130	Athens Hospital of Chest Diseases	Mina Gaga	Greece	N/A	Athens
131	General Hospital of Athens	Georgios Tatsis	Greece	N/A	Athens
132	Ospedale di Cisanello	Pier Luigi Paggiaro	Italy	N/A	Pisa
133	Azienda Ospedaliera Universitaria	Giuseppe Ugo Di Maria	Italy	IT	Catania
134	Ospedale Policlinico	Leonardo M. Fabbri	Italy	N/A	Modena
135	Azienda Ospedaliera	Antonio Foresi	Italy	N/A	Sesto San Giovanni (MI)
136	Ospedale D'Avanzo	Maria Pia Foschino	Italy	N/A	Foggia
137	Fondazione Salvatore Maugeri	Claudio Fracchia	Italy	N/A	Montescano (PV)
138	A.O.U. Arcispedale S.Anna	Alberto Papi	Italy	IT	Cona (FE)
139	Fondazione Salvatore Maugeri	Antonio Spanevello	Italy	N/A	Tradate (VA)
140	Medisch Centrum Leeuwarden	H.R. Pasma	Netherlands	N/A	Leeuwarden
141	Maxima Medisch Centrum	D.R.A.J. De Munck	Netherlands	N/A	Veldhoven
142	Sint Franciscus Gasthuis	A. Rudolphus	Netherlands	N/A	Rotterdam
143	Atrium Medisch Centrum	J.A. Noord van	Netherlands	N/A	Heerlen
144	Regional Hospital for Pulmonary Diseases	Hristo Metev	Bulgaria	N/A	Rousse
145	Multiprofile Hospital for Active Treatment	Vania Illieva-Fartunova	Bulgaria	N/A	Stara Zagora
146	Specialized Hospital for Active Treatment	Dencho Osmanliev	Bulgaria	N/A	Sofia
147	Multiprofile Hospital for Active Treatment	Evelina Troshanova	Bulgaria	N/A	Bourgas
148	Military Medical Academy	Kosta Kostov	Bulgaria	N/A	Sofia
149	Sofia District Dispensary for Pulmonary Diseases	Kiril Rashkov Palaveev	Bulgaria	N/A	Sofia
150	Medical Centre for Pneumo-Phthisiatric Diseases	Ana Dancheva	Bulgaria	N/A	Sofia
151	Multiprofile District Hospital for Active Treatment	Margarita Taseva	Bulgaria	N/A	Veliko Tarnovo
152	Pulmonology of Szarvas Ltd.	Maria Jedlinszki	Hungary	N/A	Szarvas
153	Institute of Chest Diseases of Csongrad County Municipality	Beatrix Balint	Hungary	N/A	Szeged
154	Toldy Ferenc Hospital and Out-patient Care Unit	Katalin Rajkay	Hungary	N/A	Cegled
155	Selye Janos Hospital	Judit Schlezak	Hungary	N/A	Komarom
156	Men for Care Kft. - Szazhalom Health Center	Eva Radeczky	Hungary	N/A	Szazhalombatta
157	Infer-Med Ltd.	Marta Papp	Hungary	N/A	Pecs
158	Gyogysziget, Private Praxis	Imre Meszaros	Hungary	N/A	Szigetszentmiklos
159	University School of Medical Sciences	Halina Batura-Gabryel	Poland	N/A	Poznan
160	NZOZ ALERGO-MED	Danuta Madra-Rogacka	Poland	N/A	Poznan
161	Lung Diseases Outpatient Clinic	Beata Asankowicz-Bargiel	Poland	N/A	Ostrow Wielkopolska
162	Instytut Gruzlicy i Ch. Pluc	Stefan Wesolowski	Poland	N/A	Warsaw
163	Wojewodzki Hospital	Gabriela Mieszko Filipczyk	Poland	N/A	Bytom
164	Dolnoslaskie Center of Lung Diseases	Michal Silber	Poland	N/A	Warsaw
165	Specialistyczny Zespol Gruzlicy i Chorob Pluc	Malgorzata Pawlukiewicz	Poland	N/A	Rzeszow
166	Non-public Health Care Unit ALLMED S.C.	Aleksandra Chwist-Nowak	Poland	N/A	Piekary Slaskie
167	GOU VPO St. Petersburg State Medical University	Mikhail Ilkovich	Russia	N/A	St. Petersburg
168	Medical University of Roszdrav	Alexander Zhestkov	Russia	N/A	Samara
169	Saratov State Medical University of Roszdrav	Natalia Astafyeva	Russia	N/A	Saratov
170	MUZ Clinical Hospital	Alexander Khokhlov	Russia	N/A	Yaroslavl
171	Municipal Institution of Healthcare	Nataliya Shilkina	Russia	N/A	Yaroslavl
172	Medical Academy of Roszdrav	Irina Mishina	Russia	N/A	Ivanovo
173	President's Medical Center	Elena Alekseeva	Russia	N/A	Moscow
174	Federal State Institution	Lubov Nikishenkova	Russia	N/A	Moscow
175	OOO Medical Union New Clinic	Igor Leshchenko	Russia	N/A	Ekaterinburg
176	Ukrainian State Scientific Research Inst. of Invalid Rehab.,	Sergiy Shevchuk	Ukraine	N/A	Vinnytsya
177	L.T. Malaya Institute of Therapy AMS of Ukraine	Lubov Voeykova	Ukraine	N/A	Kharkiv
178	City Clinical Hospital No. 17	Sergiy Krasnokutskiy	Ukraine	N/A	Kharkov
179	Institute of Phthisiology and Pulmonology n. a. F.G.Yanovsky	Liudmyla Iashyna	Ukraine	N/A	Kiev
180	State Medical University of Vinnitsa 'Pirogov'	Yuriy Mostovoiy	Ukraine	N/A	Vinnitsa
181	Institute of Phthisiology and Pulmonology n. a. F.G.Yanovsky	Oleksandr Dziublyk	Ukraine	N/A	Kiev
182	Regional centre of Phtysiology and Pulmonology	Mykola Ostrovskyy	Ukraine	N/A	Ivano-Frankivsk
183	Mersin Universitesi Tip Fakultesi	Sibel Atis	Turkey	N/A	Mersin
184	19 Mayis Universitesi Tip Fakultesi Gogus Hastaliklari A.B.D	Levent Erkan	Turkey	N/A	Samsun
185	Marmara Universitesi Tip Fakultesi	Sait Karakurt	Turkey	N/A	Istanbul
186	Yedikule Gogus Hastaliklari Hastanesi	Sedat Altin	Turkey	N/A	Istanbul
187	Kocaeli Universitesi Tip Fakultesi	Ahmet Ilgazli	Turkey	N/A	Izmit
188	Dr. Lutfi Kirdar Kartal Egitim ve Arastirma Hastanesi	Benan Caglayan	Turkey	N/A	Istanbul
189	Erciyes Universitesi Tip Fakultesi	Inci Gulmez	Turkey	N/A	Kayseri
190	Yedikule Gogus Hastaliklari Hastanesi	Erdogan Cetinkaya	Turkey	N/A	Istanbul
191	Ataturk Gogus Has. ve Gogus Cerrahisi	Pinar Ergun	Turkey	N/A	Ankara
192	Pamukkale Universitesi Tip Fakultesi Hastanesi	Fatma Evyapan	Turkey	N/A	Denizli
193	Ege Universitesi Tip Fakultesi Gogus Hastaliklari A.B.D.	Abdullah Sayiner	Turkey	N/A	Izmir
194	Sisli Etfal Egitim ve Arastirma Hastanesi	Ayda Damar	Turkey	N/A	Istanbul
195	Izmir Tepecik Gogus Hastaliklari ve Gogus Cerrahisi Hastanesi	Serir Aktogu	Turkey	N/A	Izmir
196	Uludag Universitesi Gogus Hastaliklari Anabilim Dali	Esra Kunt Uzaslan	Turkey	N/A	Bursa
197	Yedikule Gogus Hastaliklari Hastanesi	Saadettin Cikrikcioglu	Turkey	N/A	Istanbul
198	Dr. Suat Seren Gogus Hastaliklari ve Gogus Cerrahisi Hast.	Salih Zeki Guclu	Turkey	N/A	Izmir
199	Ankara Universitesi Tip Fakultesi Cebeci Hastanesi	Oznur Yildiz	Turkey	N/A	Ankara
200	London Chest Hospital	Prof Neil C Barnes	Great Britain	N/A	London
201	Clinical Science Centre	Peter Calverley	Great Britain	N/A	Liverpool
202	University of Cambridge School of Clinical Medicine	Edwin Roy Chilvers	Great Britain	N/A	Cambridge
203	Chesterfield Royal Hospital NHS	John William Hadfield	Great Britain	N/A	Chesterfield
204	Baillieston Health Centre	John Langan	Great Britain	N/A	Glasgow
205	Barnsley Hospital	Dr Hazim Mahdi	Great Britain	N/A	Barnsley
206	Birmingham Heartlands Hospital	Adel Mansur	Great Britain	N/A	Birmingham
207	Respiratory Medicine	Alyn Morice	Great Britain	N/A	Hull
208	West Middlesex University Hospital	Andrew Winning	Great Britain	Middlesex	Isleworth
209	Senior Clinical Lecturer in Respiratory Health	Dr Andrew M Wilson	Great Britain	N/A	Norwich
210	Belfast City Hospital	Stuart Elborn	Great Britain	N/A	Belfast
211	Sunderland Royal Hospital	Kishore Sridharan	Great Britain	N/A	Sunderland
212	Royal Hallamshire Hospital, RFU	Rod Lawson	Great Britain	N/A	Sheffield
213	Heatherwood & Wexham Park Hospitals NHS Foundation Trust	Richard Russell	Great Britain	Berks	Windsor
214	Ashford & St Peter's Hospitals NHS Foundation Trust	Monica Nordstrom	Great Britain	N/A	Chertsey
215	University of the Highlands and Islands	Douglas McKeith	Great Britain	N/A	Inverness
216	UCT Lung Institute	Eric Bateman	South Africa	N/A	Cape Town
217	Tiervlei Trial Centre	James Rattray Joubert	South Africa	N/A	Bellville
218	Gatesville Medical Centre	Ismail Abdullah	South Africa	N/A	Cape Town
219	Tygerberg Hospital	Elvis Irusen	South Africa	N/A	Tygerberg
220	Vergelegen Medi-Clinic	Jaco Jansen	South Africa	N/A	Somerset West
221	Kingsway Medical Centre	Mohamed Abdool-Gaffar	South Africa	N/A	Amanzimtoti
222	Pretoria East Hospital, Moreletapark	Gerhard Ras	South Africa	N/A	Pretoria
223	Woolcock Institute of Medical Research	Paul Seale	Australia	NSW	Glebe

1	男性或女性患者，年龄≥40岁
2	符合GOLD诊断的重度或极重度COPD的定义
3	患者目前吸烟或以前曾经吸烟，且吸烟史≥10包年
4	在最初的筛选访视（访视1）前的12个月内，患者必须至少发生过一次COPD疾病加重

1	患有COPD以外的其他重大疾病。严重的酒精和药物滥用史者
2	当前临床诊断为哮喘，经医生判断需要接受吸入型或口服糖皮质激素治疗的患者
3	曾进行肺切除胸廓造口术的患者
4	规律日间吸氧
5	近期（3个月内）发生过心肌梗塞
6	近期（ 6周内）发生呼吸道感染或COPD加重的患者
7	近期（6周内）使用过全身性糖皮质激素且用药剂量超过5mg/天者
8	近期（3个月内）发生过不稳定型或危及生命的心律失常，患者需要干预治疗或改变治疗药物
9	近期（1年内）曾因心力衰竭而住院的患者
10	当前正在接受放射治疗和化学治疗的恶性肿瘤患者
11	临床诊断为支气管扩张的患者
12	孕妇或哺乳期的妇女
13	已知对试验药物过敏
14	目前或最近（ 30天内）参加过其他临床试验
15	目前或最近( 4周内）完成肺康复项目

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