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

NCT02649998 | Withdrawn

• 1 other identifier: CRE.2015.592-T
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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. 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. 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. 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. 4.To evaluate the prognostic values of novel cardiac biomarkers on 7-day, 14-day, 30-day and 6-month mortality and readmission.

Conditions

Heart Decompensation

Keywords

Fursemide; Isosorbide Dinitrate; Heart Decompensation; Clinical Trials, Randomized; Clinical Efficacy

Outcome Measures

Primary Outcomes (1)

• 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".

  24 hour after recruitment

Secondary Outcomes (5)

• The changes in concentration of biomarkers (including BNP, NTproBNP, NGAL, hs-CRP and ST2) after randomized treatment

  24 hour after recruitment

• The changes in volume of blood pumped by the ventricle per minute (cardiac output) after randomized treatment

  24 hour after recruitment

• The number of in-hospital mortality

  An average of 5 days

• Number of day stayed in hospital

  An average of 5 days

• Number of mortality and readmission at 7-day, 14-day, 30-day and 6-month

  6-month after recruitment

Study Arms (3)

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

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

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

Drug: Furosemide; Drug: Isosorbide Dinitrate

Interventions

Furosemide DRUG

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.

Also known as: Lasix

Group 1; Group 3

Isosorbide Dinitrate DRUG

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.

Also known as: Isoket

Group 2; Group 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Shatin, NT, Hong Kong

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Furosemide; Isosorbide Dinitrate

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds; Isosorbide; Sorbitol; Sugar Alcohols; Alcohols; Carbohydrates

Study Officials

• Colin A Graham, MD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 4, 2016
• First Posted: January 8, 2016
• Study Start: January 1, 2017
• Primary Completion: December 1, 2021
• Study Completion: June 1, 2022
• Last Updated: March 21, 2023

Record last verified: 2023-03

Locations

HK (1)