Nitroglycerin vs. Furosemide Using Lung Ultrasound Pilot Trial

NCT03259165 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 17IRG33411129
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 3

Brief Summary

Nearly 80% of acute heart failure (AHF) patients admitted to the hospital are initially treated in the emergency department (ED). Once admitted, within 30 days post-discharge, 27% of patients are re-hospitalized or die. Attempts to improve outcomes with novel therapies have all failed. The evidence for existing AHF therapies are poor: No currently used AHF treatment is known to improve outcomes. ED treatment is largely the same today as 40 years ago. Congestion, such as difficulty breathing, weight gain, and leg swelling, is the primary reason why patients present to the hospital for AHF. Treating congestion is the cornerstone of AHF management. Yet half of all AHF patients leave the hospital inadequately decongested. Although it is the investigators' belief patients are often inadequately decongested in the ED, it is common teaching within emergency medicine to focus on vasodilators and avoid or minimize diuretics, especially in those patients with elevated blood pressure. This practice is largely driven by retrospective analyses or small studies suggesting vasodilators are efficacious and IV loop diuretics may be associated with harm. The evidence base to guide early ED management is poor, and the AHA/ACC guidelines provide little to no guidance for ED treatment. This reflects the lack of high quality data, a critical unmet need that the investigators will address in this study. Using clearance of LUS B-lines as the study endpoint, the investigators will study whether a diuretic intense vs. nitrate intense strategy achieves better decongestion. Although nearly two decades old, a small study of 100 patients suggested a nitrate intense strategy led to better outcomes in AHF patients with pulmonary edema when compared with a diuretic intense strategy. The investigators aim to perform a small pilot study, in hypertensive patients (SBP \> 140mmHg) to test such a strategy to inform a larger, more definitive multicenter randomized trial.

Conditions

Heart Failure; Heart Failure Acute; Acute Cardiac Failure; Acute Cardiac Pulmonary Edema

Keywords

Heart Failure; Acute Heart Failure; Pulmonary Edema; Lung Ultrasound; Extra vascular lung water; B-lines; Diuretics; Nitrates

Outcome Measures

Primary Outcomes (1)

• The Total Number of B-lines at the Conclusion of ED AHF Management

  The total number of B-lines at the conclusion of ED AHF management or maximum of 6 hours after enrollment, whichever comes first.

  During the ED phase of management, no more than 6 hours

Secondary Outcomes (2)

• Dyspnea Assessment

  During the ED phase of management, no more than 6 hours

• B-lines <= 15 at the Conclusion of ED AHF Management

  During the ED phase of management, no more than 6 hours

Other Outcomes (6)

• Total DAOOH

  Up through 30 days post discharge

• Association of B-lines at Discharge and 30-day Outcome

  Up through 30 days post discharge

• Time to Reach B-lines <15

  Throughout hospitalization, on average 5-7 days

Study Arms (2)

Nitrate Intense Strategy

EXPERIMENTAL

Patients randomized to the Nitrate intense strategy will be treated according to protocol with nitrates in combination with IV loop diuretics. This protocol only involves therapies used in everyday AHF clinical practice.

Drug: Nitrates

Diuretic Intense Strategy

EXPERIMENTAL

Patients randomized to the Diuretic intense strategy will be treated according to protocol with IV loop diuretics in combination with nitrates. This protocol only involves therapies used in everyday AHF clinical practice.

Drug: Loop Diuretics

Interventions

Nitrates DRUG

For patients randomized to the Nitrate intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first. Treatment protocol: 1. IV furosemide (unless already given) (All patients receive at minimum 20 mg IV furosemide or equivalent) 2. SL nitroglycerin (400 ucg) will be given every 5 minutes, a total of three times. (May be repeated) (Held if SBP decreases to \< 120 mmHg) 3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.

Also known as: SL or IV Nitrates

Nitrate Intense Strategy

Loop Diuretics DRUG

For patients randomized to the Diuretic intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first. Treatment protocol: 1. Patients receive 1 inch topical nitropaste 2. IV Loop diuretic dose = patients total oral dose (max dose of 200 mg IV) 3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.

Also known as: IV Loop Diuretics

Diuretic Intense Strategy

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 21 years
• Presents with shortness of breath at rest or with minimal exertion
• Clinical diagnosis of AHF and presence of \> 15 total bilateral B-lines distributed in at least 4 zones on initial LUS
• Hx of chronic HF and ANY ONE OF THE FOLLOWING:
• \[Chest radiograph consistent with AHF
• Jugular venous distension
• Pulmonary rales on auscultation
• Lower extremity edema
• BNP \> 500pg/mL\]

You may not qualify if:

• Chronic renal dysfunction, including ESRD or eGFR \< 20 ml//min/1.73m2.
• Shock of any kind. Any requirement for vasopressors or inotropes.
• SBP \< 120
• Need for immediate intubation
• Acute Coronary Syndrome OR new ST-segment elevation/depression on EKG. (troponin release outside of ACS is allowed)
• Fever \>101.5ºF
• End stage HF: transplant list, ventricular assist device
• Anemia requiring transfusion
• Known interstitial lung disease
• Suspected acute lung injury or acute respiratory distress syndrome (ARDS)
• Pregnant or recently pregnant within the last 6 months
• Severe valvular disease
• Anuria
• Allergy or hypersensitivity to nitroglycerin, furosemide or sulfa
• Concern for cardiac tamponade or restrictive cardiomyopathy

Sponsors & Collaborators

• Indiana University: lead
• Vanderbilt University: collaborator

Study Sites (3)

Eskenazi Health

Indianapolis, Indiana, 46202, United States

Location

IU Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Vanderbilt University

Nashville, Tennessee, 37235, United States

Location

MeSH Terms

Conditions

Heart Failure; Pulmonary Edema

Interventions

Nitrates; Sodium Potassium Chloride Symporter Inhibitors

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Anions; Ions; Electrolytes; Inorganic Chemicals; Nitric Acid; Nitrogen Compounds; Organic Chemicals; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Diuretics; Natriuretic Agents; Physiological Effects of Drugs

Limitations and Caveats

Due to the COVID-19 pandemic, enrollment was halted. The nature of the study was to enroll patients with AHF signs and symptoms. The principle symptom is shortness of breath, a common symptom during the peak of COVID-19. Further, employees were not allowed into the ED setting to enroll patients, when much less was known about COVID-19.

Results Point of Contact

• Title: Peter S. Pang
• Organization: Indiana University School of Medicine

ppang@iu.edu

317-880-3900

Study Officials

• Peter S Pang, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 19, 2017
• First Posted: August 23, 2017
• Study Start: December 14, 2017
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: August 20, 2024
• Results First Posted: August 20, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)