UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000019549
Receipt number R000022608
Scientific Title Multicenter Randomized controlled trial based on Balloon Pulmonary Angioplasty for chronic thromboembolic pulmonary hypertension
Date of disclosure of the study information 2015/10/28
Last modified on 2023/05/08 13:51:31

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Basic information

Public title

Multicenter Randomized controlled trial based on Balloon Pulmonary Angioplasty for chronic thromboembolic pulmonary hypertension

Acronym

Multicenter Randomized controlled trial based on Balloon Pulmonary Angioplasty for chronic thromboembolic pulmonary hypertension
(MR BPA study)

Scientific Title

Multicenter Randomized controlled trial based on Balloon Pulmonary Angioplasty for chronic thromboembolic pulmonary hypertension

Scientific Title:Acronym

Multicenter Randomized controlled trial based on Balloon Pulmonary Angioplasty for chronic thromboembolic pulmonary hypertension
(MR BPA study)

Region

Japan


Condition

Condition

Chronic thromboembolic pulmonary hypertension (CTEPH)

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

NO


Objectives

Narrative objectives1

To compare the efficacy and safety of riociguat with balloon pulmonary angioplasty (BPA) in the treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH) over the course of 12 months, to potentially aid in optimizing treatment selection and improving treatment outcomes

Basic objectives2

Safety,Efficacy

Basic objectives -Others


Trial characteristics_1


Trial characteristics_2


Developmental phase



Assessment

Primary outcomes

Change in the mean pulmonary arterial pressure from baseline to 12 months

Key secondary outcomes

1. Changes in the six-minute walk distance from baseline to 12 months
2. Changes in the Borg dyspnea index from baseline to 12 months
3. Changes in hemodynamic variables, including pulmonary vascular resistance (PVR), mean right arterial pressure, and cardiac output] from baseline to 12 months
4. Changes in the WHO functional class
5. Changes in plasma brain natriuretic peptide (BNP) levels from baseline to 12 months
6. Changes in arterial oxygen saturation (SaO2) and oxygen partial pressure (PaO2) from baseline to 12 months
7. Changes in the usage volume of oxygen therapy from baseline to 12 months, including commencing oxygen therapy due to the exacerbation of a primary disease or dosage change.
8. Changes in pulmonary function test parameters from baseline to 12 months
9. Changes in echocardiography test parameters from baseline to 12 months
10. Frequency and severity of pulmonary artery injury assessed by chest X-ray and chest computed tomography (CT) scan
11. Frequency of adverse events
12. Clinical worsening during the observation period and time to clinical worsening (TTCW)
13. Change in Quality of Life (QOL) parameters (EQ5D) from baseline to 12 months
14. Health insurance resource costs over 12 months


Base

Study type

Interventional


Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

YES

Concealment

Central registration


Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Group A: BPA treatment

Basically BPA treatment needs to be
finished within 4 months from the day of first BPA session

Interventions/Control_2

Group B: Riociguat treatment

First, starting with riociguat 3 times per day (1.0mg/time). Then increase the dose by 0.5mg every two weeks (with systolic blood pressure 95mmHg or higher).
The maximum dose is 2.5mg per dose (three times per day). Dosage is adjusted accordingly for each patient, and the adjustment is finished within 4 months from the day of starting riociguat.

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

20 years-old <=

Age-upper limit

80 years-old >

Gender

Male and Female

Key inclusion criteria

Patients meeting the following criteria will be included in the study.
(a) patients who are diagnosed with CTEPH (based on the diagnostic criteria in the 2012 Japanese Circulation Society guidelines with a WHO functional class II or III).
(b) male and female aged >= 20 years and < 80 years.
(c) patients with mean pulmonary arterial pressure of >= 25 mmHg to < 60 mmHg and pulmonary artery wedge pressure of =< 15 mmHg.
(d) patients who undergo appropriate anticoagulant therapy for at least three months prior to consent acquisition (if warfarin is used, prothrombin time-international normalized ratio should be 1.5 to 3.0).
(e) patients who provide written consent form to participate in this study after full explanation of the study.

Key exclusion criteria

Patients meeting any of the following exclusion criteria will be excluded from the trial.
(a) patients with a history of BPA.
(b) patients who underwent PEA within six months prior to consent acquisition.
(c) patients who are using unapproved pharmaceutical products.
(d) patients who used a pulmonary vasodilator within four weeks prior to the right heart catheterization after consent acquisition.
(e) patients with co-existing etiology of pulmonary hypertension other than Group 4 in the Nice Pulmonary Hypertension Classification System.
(f) patients who are pregnant or breastfeeding.
(g) patients who met the contraindication for riociguat.
(h) patients whose life expectancy is less than two years.
(i) patients who are considered to be unsuitable for participation by investigators.

Target sample size

60


Research contact person

Name of lead principal investigator

1st name Keiichi
Middle name
Last name Fukuda

Organization

Keio University School of Medicine

Division name

Department of Cardiology

Zip code

160-8582

Address

35 Shinanomachi, Shinjuku-ku, Tokyo,160-8582, Japan

TEL

03-3353-1211

Email

medgrad@info.keio.ac.jp


Public contact

Name of contact person

1st name Hiroki
Middle name
Last name Takayama

Organization

Soiken, Inc.

Division name

Division of Clinical Study Support

Zip code

101-0052

Address

4th Floor, NBF Ogawa Bld., 1-3-1 Ogawamachi, Kanda, Chiyoda-ku, Tokyo, 101-0052, Japan

TEL

03-3295-1350

Homepage URL


Email

takayama@soiken.com


Sponsor or person

Institute

Keio University School of Medicine

Institute

Department

Personal name



Funding Source

Organization

Bayer Yakuhin, Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan


Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization

the Institutional Review Board of Keio University School of Medicine

Address

35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

Tel

03-5363-3611

Email

med-rinri-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

慶應大学医学部附属病院


Other administrative information

Date of disclosure of the study information

2015 Year 10 Month 28 Day


Related information

URL releasing protocol

https://bmjopen.bmj.com/content/10/2/e028831

Publication of results

Published


Result

URL related to results and publications

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00171-0/fulltext

Number of participants that the trial has enrolled

61

Results

By month 12, the mean PAP improved by -16.3+/-1.6mmHg in the BPA group, and -7.0+/-1.5mmHg in the riociguat group (group difference, -9.3 mmHg; 95% confidence interval -12.7 - -5.9, p<0.001). BPA group also demonstrated significant improvements in SaO2, PaO2, EQ-5D-3L, and functional class, whereas the cardiac output improved significantly in the riociguat group. The BPA related complication rate was 11.6%.

Results date posted

2023 Year 05 Month 08 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics

PA group
[Age (SD)] 68.0 (9.1)
[Sex (n)] male 7 / female 24
[Hight (cm (SD))] 156.4 (10.7)
[Body weight (kg (SD))] 58.2 (10.8)
[mean pulmonary arterial pressure (mmHg (SD))] 38.1 (7.9)

Riociguat group
[Age (SD)] 65.7 (10.9)
[Sex (n)] male 3 / female 23
[Hight (cm (SD))] 154.1 (7.1)
[Body weight (kg (SD))] 56.7 (11.2)
[mean pulmonary arterial pressure (mmHg (SD))] 37.5 (8.5)

Participant flow

October 15, 2015: Protocol approval by institutional review board
April 14, 2016: First subject in
February 28, 2019: Protocol approval by certified review board
August 6, 2019: Last subject in
September 25, 2020: Last subject last visit

Adverse events

The number of patients who experienced adverse event or the disease-or-the-like throughout the study period were as follows. The disease-or-the-like was defined as adverse event, of which the causal relationship to the study treatment (BPA or riociguat) was reported not to be able to be denied.

BPA group
[Death (n (%))] 0 (0.0)
[Adverse event (n (%))] 23 (71.9)
[Serious adverse event (n (%))] 5 (15.6)
[Disease-or-the-like (n (%))] 14 (43.8)
[Serious disease-or-the-like (n (%))] 1 (3.1)

Riociguat group
[Death (n (%))] 0 (0.0)
[Adverse event (n (%))] 18 (69.2)
[Serious adverse event (n (%))] 4 (15.4)
[Disease-or-the-like (n (%))] 13 (50.0)
[Serious disease-or-the-like (n (%))] 0 (0.0)

The disease-or-the-like, which occurred after the approval by the certified review board and publication in jRCT, were as follows;

BPA group
[Disease-or-the-like (n (%))] 6 (18.8)
[Serious disease-or-the-like (n (%))] 0 (0.0)

Riociguat group
[Disease-or-the-like (n (%))] 3 (11.5)
[Serious disease-or-the-like (n (%))] 0 (0.0)

Outcome measures

<Primary endpoint>
Change in the mean pulmonary artery pressure from baseline to 12 months

<Secondary endpoint>
1. Changes in the six-minute walk distance from baseline to 12 months
2. Changes in the Borg dyspnea index from baseline to 12 months
3. Changes in hemodynamic variables, including pulmonary vascular resistance (PVR), mean right arterial pressure, and cardiac output] from baseline to 12 months
4. Changes in the WHO functional class
5. Changes in plasma brain natriuretic peptide (BNP) levels from baseline to 12 months
6. Changes in arterial oxygen saturation (SaO2) and oxygen partial pressure (PaO2) from baseline to 12 months
7. Changes in the usage volume of oxygen therapy from baseline to 12 months, including commencing oxygen therapy due to the exacerbation of a primary disease or dosage change.
8. Changes in pulmonary function test parameters from baseline to 12 months
9. Changes in echocardiography test parameters from baseline to 12 months
10. Frequency and severity of pulmonary artery injury assessed by chest X-ray and chest computed tomography (CT) scan
11. Frequency of adverse events
12. Clinical worsening during the observation period and time to clinical worsening (TTCW)
13. Change in Quality of Life parameters (EQ-5D-3L) from baseline to 12 months
14. Health insurance resource costs over 12 months

Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2015 Year 11 Month 17 Day

Date of IRB

2015 Year 10 Month 15 Day

Anticipated trial start date

2016 Year 04 Month 01 Day

Last follow-up date

2020 Year 09 Month 25 Day

Date of closure to data entry


Date trial data considered complete

2021 Year 06 Month 24 Day

Date analysis concluded

2022 Year 12 Month 31 Day


Other

Other related information



Management information

Registered date

2015 Year 10 Month 28 Day

Last modified on

2023 Year 05 Month 08 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000022608


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name