Heart DecompensationNCT02649998
Short-term Efficacy of Furosemide, Isosorbide Dinitrate and Their Combination in ADHF
A study testing Furosemide and Isosorbide Dinitrate in people with Heart Decompensation, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
Background: Acute decompensated heart failure (ADHF) is a common and potentially fatal cause of acute respiratory distress that requires immediate treatment in emergency department. The mortality rates are as high as 20% after discharge. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Decompensation
- What is being tested?
- Furosemide and Isosorbide Dinitrate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteHong Kong
- Study dates
- Jan 2017to Jun 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 18 years or older with increased dyspnoea within the previous 24 hours
- Diagnosed as heart failure by physician
Who cannot join
- Women with known or suspected pregnancy; myocardial infarction or cardiac surgery within the previous three months;
- Oxygen saturation of less than 85% on room air;
- Respiratory rate greater than 30 breaths/min;
- pH<7.35; systolic blood pressure < 110 bpm;
- Current treatment with oral nitrates in excess of 40 mg daily;
- Current treatment with oral furosemide in excess of 80 mg daily;
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- Previous adverse reaction to the study drugs;
- Requirement of noninvasive ventilation;
- Severe renal failure (creatinine >200 µmol/L)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of Short-term Efficacy of Furosemide, Isosorbide Dinitrate and Their Combination in Patients With Acute Decompensated Heart Failure: A Randomized Controlled Trial
Background:
Acute decompensated heart failure (ADHF) is a common and potentially fatal cause of acute respiratory distress that requires immediate treatment in emergency department. The mortality rates are as high as 20% after discharge. Currently, furosemide is the most commonly used medicine in emergency department for ADHF. Although nitrate was proved to generate similar effect when compared to furosemide, less than 30% of patients received nitrates. This practice happens not only in Hong Kong, but also all around the world. Moreover, there is limited evidence to support a difference in ADHF patients receiving intravenous nitrate vasodilator therapy or alternative interventions.
Read more
The aims of the study are:
- To monitor the changes in concentration of cardiac biomarkers, VAS dyspnoea score and cardiac output before and after treatment of furosemide, isosorbide dinitrate or both.
- To investigate whether the changes in concentration of cardiac biomarkers, VAS dyspnoea score and cardiac output before and after treatment is associated with the change in length of hospital stay.
- To investigate whether combination treatment with intravenous furosemide and isosorbide dinitrate in patients with HF reduces VAS dyspnoea score, in-hospital mortality, length of hospital stay and number of readmission to a higher extend than do either medication alone.
- To evaluate the prognostic values of novel cardiac biomarkers on 7-day, 14-day, 30-day and 6-month mortality and readmission.
Design:
This single-blinded randomized controlled study will be conducted in the Prince of Wales Hospital in Hong Kong.
Setting and Subjects:
Patients with dyspnoea will be screened and recruited from adult patients attending the emergency department at the Prince of Wales Hospital.
Interventions:
Patients with acute decompensated heart failure will be randomly treated with intravenous furosemide, isosorbide dinitrate or both. Level of dyspnoea, multi-biomarker and haemodynamic parameters will be measured before and after treatment.
Outcomes:
The primary outcome is the change in VAS dyspnoea score after treatment of furosemide, isosorbide dinitrate or both. The secondary outcomes are the changes in concentration of biomarkers and cardiac output, the number of in-hospital mortality, length of hospital stay, 7-day and 30-day and 6-month mortality and readmission.
Read the detailed description
Definitions:
Heart failure can be defined as an abnormality of cardiac structure or function leading to failure of the heart to deliver oxygen at a rate commensurate with the requirements of the metabolizing tissues, despite normal filling pressures (or only at the expense of increased filling pressures).
Acute decompensated Heart Failure (ADHF), is defined according to Framingham criteria as a change in symptoms and signs in the context of heart failure. For this study we define this as an acute change in symptoms and signs within the previous 24 hours.
In the New York Heart Association classification (NYHA), Class I: no limitation is experienced in any activities; there are no symptoms from ordinary activities.; Class II: slight, mild limitation of activity; the patient is comfortable at rest or with mild exertion.; Class III: marked limitation of any activity; the patient is comfortable only at rest.; Class IV: any physical activity brings on discomfort and symptoms occur at rest.
- Conditions
- Heart Decompensation
- Being tested
- Furosemide, Isosorbide Dinitrate
- Keywords
- Fursemide, Isosorbide Dinitrate, Heart Decompensation, Clinical Trials, Randomized, Clinical Efficacy
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FurosemideDrug
Also called Lasix
Furosemide is the most commonly used medication for treatment of heart failure. It causes a direct vasodilator effect shortly after administration, followed by diuresis induction. However, furosemide also activates both the sympathetic and the renin angiotensin systems, causing a rise in peripheral resistance.
Isosorbide DinitrateDrug
Also called Isoket
Isosorbide dinitrate is a vasodilator which is also well-known for treating acute decompensated heart failure. It induces acute venodilatation at low dose and arteries dilation when gradually increasing the dose. The effect peaks 5 min after administration.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Active comparator | Each patient will initially receive a 40 mg bolus of IV furosemide (10 mg/mL) and a 2 mL bolus of IV saline placebo, followed by IV saline placebo 6 mL/h Receives: Drug: Furosemide |
| Group 2 | Active comparator | Each patient will initially receive a bolus of IV saline placebo and a 2 mL bolus of IV isosorbide dinitrate (1 mg/mL), followed by IV isosorbide dinitrate 6 mL/h Receives: Drug: Isosorbide Dinitrate |
| Group 3 | Active comparator | Each patient will initially receive a 40 mg bolus of IV furosemide (10 mg/mL) and a 2 mL bolus of IV isosorbide dinitrate (1 mg/mL), followed by IV isosorbide dinitrate 6 mL/h Receives: Drug: Furosemide; Drug: Isosorbide Dinitrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
The change in VAS dyspnoea score after randomized treatment
Patients will be asked to indicate their status of dyspnoea using a visual analogue scale (VAS). They will be asked to make a mark on a 100 mm uncalibrated horizontal line in sitting (patients head at ≥ 600 relative to horizontal) and supine positions. The mark will be converted to a score (0-100 points) by measuring the distance from the left end. A VAS dyspnoea score of 0 corresponds to the patient's subjective feeling of "I can breathe normally" and a score of 100 represent to "I cannot breathe at all".
Measured: 24 hour after recruitment
Secondary outcomes (5)
The changes in concentration of biomarkers (including BNP, NTproBNP, NGAL, hs-CRP and ST2) after randomized treatment
5mL venous blood will be collected and applied to BNP, NTproBNP, NGAL and hs-CRP rapid test at baseline, 3 hours and 24 hours after randomized treatment at ED. The remaining blood will be centrifuged and stored at -20oC for ST2 measurement.
Measured: 24 hour after recruitment
The changes in volume of blood pumped by the ventricle per minute (cardiac output) after randomized treatment
The cardiac output will be measured using an ultrasonic cardiac output monitor at baseline, 3 hours and 24 hours after randomized treatment at ED.
Measured: 24 hour after recruitment
The number of in-hospital mortality
Measured: An average of 5 days
Number of day stayed in hospital
Measured: An average of 5 days
Number of mortality and readmission at 7-day, 14-day, 30-day and 6-month
Measured: 6-month after recruitment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2016 (estimated)
- Study startJan 2017
- Primary completionDec 2021 (estimated)
- Study completionJun 2022 (estimated)
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart DecompensationStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Colin Graham, Chinese University of Hong Kong
- Investigators
- Colin A Graham, MD, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02649998
- Sponsor's protocol ID
- CRE.2015.592-T
- Status last verified
- Mar 2023
- First submitted
- 4 Jan 2016
- Last updated
- 21 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Short-term Efficacy of Furosemide, Isosorbide Dinitrate and Their Combination in Patients With Acute Decompensated Heart Failure: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT02649998
- Acronym / sponsor ID
- CRE.2015.592-T
- Conditions
- Heart Decompensation
- Keywords
- Fursemide, Isosorbide Dinitrate, Heart Decompensation, Clinical Trials, Randomized, Clinical Efficacy
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- Jan 2017
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Jun 2022 (estimated)
- First posted
- 8 Jan 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Acute decompensated heart failure (ADHF) is a common and potentially fatal cause of acute respiratory distress that requires immediate treatment in emergency department. The mortality rates are as high as 20% after discharge. Currently, furosemide is the most commonly used medicine in emergency department for ADHF. Although nitrate was proved to generate similar effect when compared to furosemide, less than 30% of patients received nitrates. This practice happens not only in Hong Kong, but also all around the world. Moreover, there is limited evidence to support a difference in ADHF patients receiving intravenous nitrate vasodilator therapy or alternative interventions.
The aims of the study are:
- To monitor the changes in concentration of cardiac biomarkers, VAS dyspnoea score and cardiac output before and after treatment of furosemide, isosorbide dinitrate or both.
- To investigate whether the changes in concentration of cardiac biomarkers, VAS dyspnoea score and cardiac output before and after treatment is associated with the change in length of hospital stay.
- To investigate whether combination treatment with intravenous furosemide and isosorbide dinitrate in patients with HF reduces VAS dyspnoea score, in-hospital mortality, length of hospital stay and number of readmission to a higher extend than do either medication alone.
- To evaluate the prognostic values of novel cardiac biomarkers on 7-day, 14-day, 30-day and 6-month mortality and readmission.
Design:
This single-blinded randomized controlled study will be conducted in the Prince of Wales Hospital in Hong Kong.
Setting and Subjects:
Patients with dyspnoea will be screened and recruited from adult patients attending the emergency department at the Prince of Wales Hospital.
Interventions:
Patients with acute decompensated heart failure will be randomly treated with intravenous furosemide, isosorbide dinitrate or both. Level of dyspnoea, multi-biomarker and haemodynamic parameters will be measured before and after treatment.
Outcomes:
The primary outcome is the change in VAS dyspnoea score after treatment of furosemide, isosorbide dinitrate or both. The secondary outcomes are the changes in concentration of biomarkers and cardiac output, the number of in-hospital mortality, length of hospital stay, 7-day and 30-day and 6-month mortality and readmission.
Detailed description
Definitions:
Heart failure can be defined as an abnormality of cardiac structure or function leading to failure of the heart to deliver oxygen at a rate commensurate with the requirements of the metabolizing tissues, despite normal filling pressures (or only at the expense of increased filling pressures).
Acute decompensated Heart Failure (ADHF), is defined according to Framingham criteria as a change in symptoms and signs in the context of heart failure. For this study we define this as an acute change in symptoms and signs within the previous 24 hours.
In the New York Heart Association classification (NYHA), Class I: no limitation is experienced in any activities; there are no symptoms from ordinary activities.; Class II: slight, mild limitation of activity; the patient is comfortable at rest or with mild exertion.; Class III: marked limitation of any activity; the patient is comfortable only at rest.; Class IV: any physical activity brings on discomfort and symptoms occur at rest.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Active comparator | Drug: FurosemideEach patient will initially receive a 40 mg bolus of IV furosemide (10 mg/mL) and a 2 mL bolus of IV saline placebo, followed by IV saline placebo 6 mL/h |
| Group 2 | Active comparator | Drug: Isosorbide DinitrateEach patient will initially receive a bolus of IV saline placebo and a 2 mL bolus of IV isosorbide dinitrate (1 mg/mL), followed by IV isosorbide dinitrate 6 mL/h |
| Group 3 | Active comparator | Drug: Furosemide, Drug: Isosorbide DinitrateEach patient will initially receive a 40 mg bolus of IV furosemide (10 mg/mL) and a 2 mL bolus of IV isosorbide dinitrate (1 mg/mL), followed by IV isosorbide dinitrate 6 mL/h |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients aged 18 years or older with increased dyspnoea within the previous 24 hours
- Diagnosed as heart failure by physician
Key exclusion criteria (9 listed)
- Women with known or suspected pregnancy; myocardial infarction or cardiac surgery within the previous three months;
- Oxygen saturation of less than 85% on room air;
- Respiratory rate greater than 30 breaths/min;
- pH<7.35; systolic blood pressure < 110 bpm;
- Current treatment with oral nitrates in excess of 40 mg daily;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FurosemideAlso: LasixFurosemide is the most commonly used medication for treatment of heart failure. It causes a direct vasodilator effect shortly after administration, followed by diuresis induction. However, furosemide also activates both the sympathetic and the renin angiotensin systems, causing a rise in peripheral resistance. | Drug | Group 1, Group 3 |
| Isosorbide DinitrateAlso: IsoketIsosorbide dinitrate is a vasodilator which is also well-known for treating acute decompensated heart failure. It induces acute venodilatation at low dose and arteries dilation when gradually increasing the dose. The effect peaks 5 min after administration. | Drug | Group 2, Group 3 |
Primary outcome
The change in VAS dyspnoea score after randomized treatment
Time frame: 24 hour after recruitment
Patients will be asked to indicate their status of dyspnoea using a visual analogue scale (VAS). They will be asked to make a mark on a 100 mm uncalibrated horizontal line in sitting (patients head at ≥ 600 relative to horizontal) and supine positions. The mark will be converted to a score (0-100 points) by measuring the distance from the left end. A VAS dyspnoea score of 0 corresponds to the patient's subjective feeling of "I can breathe normally" and a score of 100 represent to "I cannot breathe at all".
5 secondary outcomes
The changes in concentration of biomarkers (including BNP, NTproBNP, NGAL, hs-CRP and ST2) after randomized treatment
Time frame: 24 hour after recruitment
The changes in volume of blood pumped by the ventricle per minute (cardiac output) after randomized treatment
Time frame: 24 hour after recruitment
The number of in-hospital mortality
Time frame: An average of 5 days
Number of day stayed in hospital
Time frame: An average of 5 days
Number of mortality and readmission at 7-day, 14-day, 30-day and 6-month
Time frame: 6-month after recruitment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Colin A Graham, MD principal investigator
Chinese University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Furosemide and Isosorbide Dinitrate in people with Heart Decompensation, run by Chinese University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 21 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The change in VAS dyspnoea score after randomized treatment (time frame: 24 hour after recruitment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2023.