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Short-term Efficacy of Furosemide, Isosorbide Dinitrate and Their Combination in ADHF

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ClinicalTrials.gov Identifier: NCT02649998
Recruitment Status : Suspended (Awaiting for funding)
First Posted : January 8, 2016
Last Update Posted : February 1, 2019
Sponsor:
Information provided by (Responsible Party):
Colin Graham, Chinese University of Hong Kong

Brief 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. 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:

  1. 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.
  2. 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.
  3. 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.
  4. 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.


Condition or disease Intervention/treatment Phase
Heart Decompensation Drug: Furosemide Drug: Isosorbide Dinitrate Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 174 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
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
Study Start Date : January 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Active Comparator: Group 1
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
Drug: Furosemide
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.
Other Name: Lasix

Active Comparator: Group 2
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
Drug: Isosorbide Dinitrate
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.
Other Name: Isoket

Active Comparator: Group 3
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
Drug: Furosemide
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.
Other Name: Lasix

Drug: Isosorbide Dinitrate
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.
Other Name: Isoket




Primary Outcome Measures :
  1. 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".


Secondary Outcome Measures :
  1. The changes in concentration of biomarkers (including BNP, NTproBNP, NGAL, hs-CRP and ST2) after randomized treatment [ Time Frame: 24 hour after recruitment ]
    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.

  2. The changes in volume of blood pumped by the ventricle per minute (cardiac output) after randomized treatment [ Time Frame: 24 hour after recruitment ]
    The cardiac output will be measured using an ultrasonic cardiac output monitor at baseline, 3 hours and 24 hours after randomized treatment at ED.

  3. The number of in-hospital mortality [ Time Frame: An average of 5 days ]
  4. Number of day stayed in hospital [ Time Frame: An average of 5 days ]
  5. Number of mortality and readmission at 7-day, 14-day, 30-day and 6-month [ Time Frame: 6-month after recruitment ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged 18 years or older with increased dyspnoea within the previous 24 hours
  • Diagnosed as heart failure by physician

Exclusion Criteria:

  • 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;
  • Previous adverse reaction to the study drugs;
  • Requirement of noninvasive ventilation;
  • Severe renal failure (creatinine >200 µmol/L)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02649998


Locations
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Hong Kong
Prince of Wales Hospital
Sha Tin, NT, Hong Kong
Sponsors and Collaborators
Chinese University of Hong Kong
Investigators
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Principal Investigator: Colin A Graham, MD Chinese University of Hong Kong

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Responsible Party: Colin Graham, Professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT02649998     History of Changes
Other Study ID Numbers: CRE.2015.592-T
First Posted: January 8, 2016    Key Record Dates
Last Update Posted: February 1, 2019
Last Verified: January 2019
Keywords provided by Colin Graham, Chinese University of Hong Kong:
Fursemide
Isosorbide Dinitrate
Heart Decompensation
Clinical Trials, Randomized
Clinical Efficacy
Additional relevant MeSH terms:
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Furosemide
Heart Failure
Heart Diseases
Cardiovascular Diseases
Isosorbide
Isosorbide Dinitrate
Isosorbide-5-mononitrate
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Diuretics, Osmotic
Vasodilator Agents
Nitric Oxide Donors