An observational study of chronic heart failure patients receiving ivabradine
| ISRCTN | ISRCTN11703380 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11703380 |
| Secondary identifying numbers | IC4-16257-004-CHN |
- Submission date
- 20/10/2016
- Registration date
- 08/11/2016
- Last edited
- 16/06/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
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 June 2021
Who is funding the study?
Servier (Tianjin) Pharmaceutical Co., Ltd (China)
Who is the main contact?
Dr Qiaohui Kang, qiaohui.kang@servier.com
Contact information
Scientific
6th Floor
West Building
World Financial Center
No. 1, East 3rd Ring Middle Road
Chaoyang District
Beijing
100020
China
| Phone | +86 10 65610341 Ext 612 |
|---|---|
| qiaohui.kang@servier.com |
Study information
| Study design | Prospective multicentre single-arm observational study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Single-arm study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | POSITIVE: POSt-authorization drug Intensive surveillance monitoring sTudy of IVabradine efficacy and safety in patients with chronic heart failurE |
| Study acronym | POSITIVE |
| Study objectives | To assess the efficacy and safety of Corlentor®(ivabradine) in Chinese chronic heart failure patients. |
| Ethics approval(s) | Ethics committee of Zhongshan Hospital Fudan University, 12/09/2016, ref: B2016-118 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Corlentor® (Ivabradine) |
| Primary outcome measure | 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 study start date | 31/12/2016 |
| Completion date | 30/06/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 3300 |
| Total final enrolment | 1003 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 31/12/2016 |
| Date of final enrolment | 17/07/2020 |
Locations
Countries of recruitment
- China
Study participating centres
200032
China
China
Sponsor information
Industry
6th Floor
West Building
World Financial Center
No. 1, East 3rd Ring Middle Road
Chaoyang District
Beijing
100020
China
| Website | http://www.servier.com/ |
|---|---|
"ROR" |
https://ror.org/00fan0f25 |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 30/06/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Current publication and dissemination plan as of 09/06/2021: Planned publication in a high impact peer reviewed journal Previous 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. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Interim results article | 08/12/2021 | 09/12/2021 | Yes | No |
Editorial Notes
16/06/2023: The following changes were made to the trial record:
1. The contact was changed.
2. The intention to publish date was changed from 31/12/2022 to 30/06/2024.
16/12/2021: The intention to publish date was changed from 31/12/2021 to 31/12/2022.
09/12/2021: Publication reference added.
09/06/2021: The following changes have been made:
1. The recruitment end date has been changed from 31/07/2019 to 17/07/2020.
2. The overall trial end date has been changed from 31/05/2020 to 30/06/2021 and the plain English summary has been updated to reflect this change.
3. The intention to publish date has been changed from 31/05/2021 to 31/12/2021.
4. The total final enrolment number has been added.
5. The trial participating centre "80 sites in China" has been changed to "72 sites in China".
6. The publication and dissemination plan has been updated.
30/10/2019: The scientific contact detail's details have been changed and the plain English summary updated accordingly.
30/08/2018: Contact details updated.
10/08/2018: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/06/2018 to 31/07/2019.
2. The overall trial end date was changed from 31/12/2018 to 31/05/2020.
3. The intention to publish date was changed from 31/12/2019 to 31/05/2021.
31/10/2017: Internal review.
