Clinical trial NCT02649998: Short-term Efficacy of Furosemide, Isosorbide Dinitrate and Their Combination in ADHF
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 type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Heart Decompensation
Keywords: Fursemide
Isosorbide Dinitrate
Heart Decompensation
Clinical Trials, Randomized
Clinical Efficacy
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2016-01-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: The change in VAS dyspnoea score after randomized treatment
timeFrame: 24 hour after recruitment
Secondary outcomes:
measure: The changes in concentration of biomarkers (including BNP, NTproBNP, NGAL, hs-CRP and ST2) after randomized treatment
timeFrame: 24 hour after recruitment
measure: The changes in volume of blood pumped by the ventricle per minute (cardiac output) after randomized treatment
timeFrame: 24 hour after recruitment
measure: The number of in-hospital mortality
timeFrame: An average of 5 days
measure: Number of day stayed in hospital
timeFrame: An average of 5 days
measure: Number of mortality and readmission at 7-day, 14-day, 30-day and 6-month
timeFrame: 6-month after recruitment
Other outcomes:
Locations:
city: Sha Tin
country: Hong Kong
facility: Prince of Wales Hospital
state: NT
Study officials:
affiliation: Chinese University of Hong Kong
name: Colin A Graham, MD
role: PRINCIPAL_INVESTIGATOR
References: