UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Early intervention for mild or borderline pulmonary arterial hypertension (PAH) associated with connective tissue diseases
Title of the study (Brief title)	Keio university clinical trial for early pulmonary arterial hypertension with connective tissue diseases (KEEP-ACTIVE study)
Region	Japan

Condition
Condition	Pulmonary arterial hypertension (PAH) associated with connective tissue disease
Classification by specialty	Cardiology Clinical immunology
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	Connective tissue diseases (CTD) are categorized as systemic inflammatory disorders characterized by autoimmune phenomena. Pulmonary arterial hypertension (PAH) is one of life-threatening manifestations of CTD, whose histological features are thickening of pulmonary artery walls. The treatment is often difficult, and its outcome is very poor because of progressive right ventricular failure and low cardiac output. Recently, novel drugs, including prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors, have been developed and are available for treatment for idiopathic PAH and PAH associated with CTD. Rationales for these treatments are mainly based on results of clinical trials enrolling patients with severe PAH classified as having WHO functional class III or IV. Despite these novel options, PAH is still one of leading causes of death in patients with CTD, including systemic sclerosis and mixed connective tissue disease. Thus, significance of early intervention for these patients is now on dispute. However, there is no evidence for the efficacy of early intervention to PAH in modifying a natural course of PAH-CTD. In this study, Sildenafil is selected as a candidate drug for early intervention to PAH-CTD. As a control drug we use Beraprost, which is commonly used for the treatment of peripheral vascular disease associated with CTD in Japan. Also we analyze the effect of PAH drugs for peripheral vascular disease.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Time to clinical worsening
Key secondary outcomes

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Beraprost sodium
Interventions/Control_2	Beraprost sodium and Sildenafil citrate
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	80 years-old >
Gender	Male and Female
Key inclusion criteria	1)Patients who are followed up at institutions in which this clinical trial is exected. 2)Patients who fulfill the classification criteria of collagen diseases such as SLE, SSc, PM/DM, and MCTD. 3)Mean pulmonary arterial pressure is over 20 mmHg and PCWP is less than 15 measured by right heart catheterization. 4) Patients classified as WHO functional class I or II
Key exclusion criteria	1) Hypersensitivity to Sildenafil or Beraprost. 2) Patients with chronic pulmonary thromboembolism. 3) Patients who will be on home oxygen therapy 4) Patients who will be classified as WHO class III or IV 5) Patients with severe ischemic heart diseases or cardiomyopathy 6) Patients with malignancy
Target sample size	70

Research contact person
Name of lead principal investigator	Masataka Kuwana
Organization	Department of Internal Medicine, Keio University School of Medicine
Division name	Division of Rheumatology
Address	35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JAPAN
TEL	03-3353-1211
Email	kuwanam@z5.keio.jp

Public contact
Name of contact person	Hidekata Yasuoka
Organization	Department of Internal Medicine, Keio University School of Medicine
Division name	Division of Rheumatology
Address	35 Shinanomachi, Shinjuku, Tokyo, Japan
TEL	03-3353-1211
Homepage URL
Email	yasuokah@z8.keio.jp

Sponsor
Institute	Keio University
Institute
Department

Funding Source
Organization	KEEP-ACTIVE study group
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

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	亀田総合病院（千葉県）、川崎市立井田病院（神奈川県）、川崎市立川崎病院（神奈川県）、慶應義塾大学病院（東京都）、国立病院機構東京医療センター（東京都）、埼玉医科大学総合医療センター（埼玉県）、聖路加国際病院（東京都）、東京歯科大学市川総合病院（東京都）、東京女子医科大学病院（東京都）、東京都立大塚病院（東京都）、聖マリアンナ医科大学（神奈川県）、北里大学（神奈川県）

Other administrative information
Date of disclosure of the study information	2008 Year 10 Month 01 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2008 Year 08 Month 25 Day
Anticipated trial start date	2008 Year 09 Month 01 Day
Last follow-up date	2018 Year 03 Month 31 Day
Date of closure to data entry	2018 Year 03 Month 31 Day
Date trial data considered complete	2018 Year 03 Month 31 Day
Date analysis concluded	2018 Year 09 Month 01 Day

Related information
URL releasing protocol
Publication of results	Partially published
URL releasing results
Results
Other related information

Management information
Registered date	2008 Year 09 Month 02 Day
Last modified on	2018 Year 03 Month 12 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000001589