Condition category
Circulatory System
Date applied
20/10/2016
Date assigned
08/11/2016
Last edited
08/11/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Heart failure means that the heart has become too weak or stiff and is unable to pump blood around the body. The annual mortality (death) rate of heart failure patients is over 20% despite receiving treatment. Higher heart rate is a risk factor for poor outcome, but heart rate reduction is often insufficient in such patients. The drug ivabradine (Corlentor®) improves heart function as well as long-term survival in chronic heart failure patients with reduced left ventricular ejection fraction (i.e. the amount of blood pumped out of the heart) through specifically heart rate reduction, and is recommended in the heart failure treatment guidelines of Europe, America and China. Since Corlentor® was just approved by Chinese food and drug administration (CFDA) in April 2015, more clinical information needs to be collected during practice in China. The aim of this study is to assess how well Corlentor® works and its safety in Chinese heart failure patients.

Who can participate?
Patients aged over 18 with chronic heart failure and reduced left ventricular ejection fraction whose resting heart rate is 75 beats per minute or over, and who have been prescribed Corlentor® before entering the study

What does the study involve?
All patients are asked to come to follow-up visits after four weeks and then after another five months. During these visits a routine practice investigation is carried out. A quality of life questionnaire is completed and the safety and tolerability of Corlentor® is measured and evaluated during the follow-up visits. The dosage of Corlentor® can be adapted or even discontinued if needed during the follow-up period according to heart rate reduction, but the follow-up visits continue as scheduled regardless of whether the Corlentor® is taken or not.

What are the possible benefits and risks of participating?
Corlentor® may relieve heart failure symptoms, improve heart function and quality of life, and reduce the re-hospitalization and/or death rate. Close follow-up by investigators during the study may also provide additional benefit to the participants. Corlentor® has been used worldwide since 2005 and was approved in China in 2015, and the possible side effects include phosphenes (visual disturbances) and bradycardia (slow heart rate).

Where is the study run from?
About 80 hospitals all over China, with Zhongshang Hospital Fudan University as the leading site.

When is the study starting and how long is it expected to run for?
December 2016 to December 2018

Who is funding the study?
Servier (Tianjin) Pharmaceutical Co., Ltd (China)

Who is the main contact?
Dr Xiaoxing Zhang
Xiaoxing.zhang@servier.com

Trial website

Contact information

Type

Scientific

Primary contact

Dr Xiaoxing Zhang

ORCID ID

Contact details

6th Floor
West Building
World Financial Center
No. 1
East 3rd Ring Middle Road
Chaoyang District
Beijing
100020
China

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

IC4-16257-004-CHN

Study information

Scientific title

POSITIVE: POSt-authorization drug Intensive surveillance monitoring sTudy of IVabradine efficacy and safety in patients with chronic heart failurE

Acronym

POSITIVE

Study hypothesis

To assess the efficacy and safety of Corlentor®(ivabradine) in Chinese chronic heart failure patients.

Ethics approval

Ethics committee of Zhongshan Hospital Fudan University, 12/09/2016, ref: B2016-118

Study design

Prospective multicentre single-arm observational study

Primary study design

Observational

Secondary study design

Single-arm study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Chronic heart failure

Intervention

This study enrolls patients who have already been administered the study drug in line with the indication described on the label based on the doctor’s decision. After that, the investigator collects information during the follow-up period (1-month and 6-month visits). The study drug dose is adjusted or discontinued based on the doctor’s judgement during the follow-up period. Follow-up continues until the 6-month visit regardless of the study drug use.

The study drug (Corlentor®) should be used following the description of the label. 5 mg bid is the recommended starting dose, but the starting dose can be changed based on the patient’s situation and adjusted during the follow-up period. It is recommended on the label that a 2.5 mg bid starting dose should be considered in patients aged over 75, with dose adjustment based on the patient's heart rate (because the direct efficacy of Corlentor® is heart rate reduction), and the maximum dose should not exceed 7.5 mg bid during long-term use.

Intervention type

Drug

Phase

Not Applicable

Drug names

Corlentor® (Ivabradine)

Primary outcome measures

Heart rate change after Corlentor® administration, measured using office daytime resting heart rate (heart rate and rhythm from the 12-lead ECG will also be considered for double-confirm if available) at the 1-month and 6-month visit

Secondary outcome measures

Measured at the 1-month and 6-month visit:
1. Heart failure symptoms, measured based on the inquisition and physical examination carried out by cardiologists
2. Left ventricular function, measured by echocardiogram
3. Heart failure biomarker (BNP and/or NT-proBNP), assessed with a routine laboratory test
4. Quality of life, assessed by KCCQ questionnaire
5. Safety and tolerability of Corlentor®, measured through monitoring adverse drug reactions and changes of laboratory indicators after administration of the drug

Overall trial start date

31/12/2016

Overall trial end date

31/12/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male or female, outpatients or inpatients, over 18 (inclusive) years old
2. Sinus rhythm
3. Resting heart rate ≥75 bpm as measured by 12-lead ECG prior to enrollment
4. Chronic heart failure patients with systolic dysfunction (the left ventricular ejection fraction (LVEF) was ≤ 40 % in the last 3 months)
5. Patients whose cardiac function classification according to the New York Heart Association (NYHA) standard are class 2-4
6. Patients who have received standard treatment (including β-blockers) for heart failure, or are intolerable or contraindicated to β-blockers
7. Patients who meet the indication of Corlentor® and are starting to receive Corlentor® treatment
8. Patients who have signed the informed consent forms

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

3300

Participant exclusion criteria

1. Patients who have received the treatment with Corlentor® within 2 weeks
2. Recent (<1 month) occurrence of acute myocardial infarction
3. Acute heart failure and cardiogenic shock
4. Sick sinus syndrome or sino-atrial block
5. Third-degree atrioventricular block
6. Severe hypotension (<90/50 mmHg)
7. Severe liver dysfunction (Child-Pugh score ≥10)
8. End-stage renal failure (Plasma creatinine clearance <15 ml/min)
9. Pregnancy, lactation and women of child-bearing potential not using appropriate contraceptive measures
10. Patients unable to visit as scheduled

Recruitment start date

31/12/2016

Recruitment end date

30/06/2018

Locations

Countries of recruitment

China

Trial participating centre

Zhongshang Hospital Fudan University (leading site)
Shanghai
200032
China

Trial participating centre

80 sites in China
-

Sponsor information

Organisation

Servier (Tianjin) Pharmaceutical Co., Ltd

Sponsor details

6th Floor
West Building
World Financial Center
No. 1
East 3rd Ring Middle Road
Chaoyang District
Beijing
100020
China

Sponsor type

Industry

Website

http://www.servier.com/

Funders

Funder type

Industry

Funder name

Servier (Tianjin) Pharmaceutical Co., Ltd

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

IPD sharing plan
The datasets generated and/or analysed during the current study are available from Prof. Junbo Ge (ge.junbo@zs-hospital.sh.cn) on reasonable request

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes