Sodium NItroPrusside Treatment in Acute Heart Failure (SNIP-AHF)

Sodium NItroPrusside Treatment in Acute Heart Failure: Multicenter, Observational, Retrospective Study

The primary objective of this multicentric observational retrospective study is to assess the efficacy and safety of SNP as part of the treatment regimen of AHF patients and to identify predictors of efficacy. The primary efficacy endpoint is brain natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT-proBNP) reduction (at least 25% from baseline levels) 48 hours after initiation of SNP infusion. AHF presentation (de novo or ADHF), systolic blood pression at presentation, left ventricle ejection fraction and dimension, entity of mitral regurgitation and central venous pressure will be evaluated in order to identify predictors of efficacy of SNP (in terms of primary endpoint).

Study Overview

• Status: Completed
• Conditions: Acute Heart Failure
• Intervention / Treatment: Drug: SNP - Sodium Nitroprusside

Detailed Description

The present is a multicenter, observational, retrospective study. All consecutive patients admitted with a diagnosis of AHF to the Cardiothoracovascular Departments of the ASST Grande Ospedale Metropolitano Niguarda (Milan), ASST Ospedale Papa Giovanni XXIII (Bergamo) and Ospedale Le Molinette (Torino), and treated with intravenous SNP between January 2016 and January 2020 will be included, and medical records screened. Through the collaboration of the two joining institution, the investigator plan to include approximately 300 patients. Inclusion criteria are: age 18 years or older; AHF diagnosis, defined as rapid onset or worsening of symptoms and/or signs of HF; Intravenous SNP treatment. Exclusion criteria are: Age <18 years old; AHF after cardiac surgery; AHF complicated by cardiogenic shock requiring high dosage (defined as inotropic score >10) vasoactive agents and/or short-term extracorporeal life support (i.e. VA-ECMO, Impella). Inotropic score (IS) calculated as: dopamine dose (μg/kg/min) + dobutamine dose (μg/kg/min) + 100 × epinephrine dose (μg/kg/min) + 100 × norepinephrine dose (μg/kg/min) + 10 × phosphodiesterase 3 inhibitor dose (μg/kg/min). Invasive monitoring of central venous pressure (CVP) and arterial pressure may be present. The Swan Ganz pulmonary artery catheter for continuous haemodynamic monitoring will be rarely used. Simultaneous intravenous diuretics and concomitant inotropic agents with a maximun IS<20 administration will be tolerated. SNP will be administered intravenously by a continuous infusion at a dose of 0.2 up to 2 mcg/kg/min. Titration of SNP up to the maximum tolerated dose will be based on achieving decongestion, defined as decrease in CVP and reduction of pulmonary congestion, with a target mean arterial pressure of 65 to 70 mmHg. Headache or severe hypotension, as well as documented thiocyanate toxicity, will warrant discontinuation of SNP therapy. The primary objective of our study is to assess the efficacy and safety of SNP as part of the treatment regimen of AHF patients and to identify predictors of efficacy. The primary efficacy endpoint is brain natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT-proBNP) reduction (at least 25% from baseline levels) 48 hours after initiation of SNP infusion. Secondary endpoints include: Survival free from rehospitalization for HF at 6 months; 30-day and 6-month mortality; Composite of long-term LVAD implantation or HTx at 30 days and 6 months; Length of intensive care unit and total hospital stay. Safety endpoints are: thiocyanate toxicity, headache, severe hypotension requiring discontinuation of therapy, ventricular arrhythmias The investigators will evaluate the following baseline patients' characteristics in order to identify predictors of efficacy of SNP (in terms of primary endpoint): AHF presentation (de novo or ADHF); SBP at presentation (preserved, i.e. 90-140 mmHg; elevated, i.e. >140 mmHg; low, <90 mmHg); left ventricle ejection fraction (LVEF), graded as reduced (<40%), mid-range (40-49%) or preserved (≥50%); end-diastolic diameter (EDD); entity of mitral regurgitation (none/mild or moderate/severe mitral regurgitation); CVP (< 8 mmHg or ≥8 mmHg) Patient demographics, haemodynamics, laboratory values, echocardiographic parameters, adverse events and clinical outcomes will be obtained by complete chart review.

• Study Type: Observational
• Enrollment (Actual): 200

Contacts and Locations

Study Locations

• Italy
  • Italia
    • Milano, Italia, Italy, 20162
      • ASST Grande Ospedale Metropolitano Niguarda

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All consecutive patients admitted with a diagnosis of AHF to the Cardiothoracovascular Departments of the ASST Grande Ospedale Metropolitano Niguarda (Milan), ASST Ospedale Papa Giovanni XXIII (Bergamo) and Ospedale Le Molinette (Torino), and treated with intravenous SNP between January 2016 and January 2020 will be included, and medical records screened. Through the collaboration of the two joining institution, we plan to include approximately 300 patients.

Description

Inclusion Criteria:

• Age 18 years or older
• AHF diagnosis, defined as rapid onset or worsening of symptoms and/or signs of HF. According to a recently proposed new definition, HF is a clinical syndrome with current or prior Symptoms and or signs caused by a structural and/or functional cardiac abnormality (as determined by EF <50%, abnormal cardiac chamber enlargement, E/E' >15, moderate/severe ventricular hypertrophy or moderate/severe valvular obstructive or regurgitant lesion) and corroborated by at least one of the following: Elevated natriuretic peptide levels ; Objective evidence of cardiogenic pulmonary or systemic congestion by diagnostic modalities such as imaging (e.g. by chest X-ray or elevated filling pressures by echocardiography) or haemodynamic measurement (e.g. right heart catheterization, pulmonary artery catheter) at rest or with provocation (e.g. exercise).
• Intravenous SNP treatment

Exclusion Criteria:

• Age <18 years old
• AHF after cardiac surgery
• AHF complicated by cardiogenic shock requiring high dosage (defined as inotropic score >10) vasoactive agents and/or short-term extracorporeal life support (i.e. VA-ECMO, Impella). Inotropic score (IS) calculated as: dopamine dose (μg/kg/min) + dobutamine dose (μg/kg/min) + 100 × epinephrine dose (μg/kg/min) + 100 × norepinephrine dose (μg/kg/min) + 10 × phosphodiesterase 3 inhibitor dose (μg/kg/min).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acute heart Failure AHF; AHF diagnosis, defined as rapid onset or worsening of symptoms and/or signs of HF	Drug: SNP - Sodium Nitroprusside; The primary objective of our study is to assess the efficacy and safety of SNP as part of the treatment regimen of AHF patients and to identify predictors of efficacy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NT-pro-BNP or BNP reduction	Significant reduction (at least 25% from baseline levels) 48 hours after initiation of SNP infusion	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalizations	Survival free from re-hospitalizations for heart failure	6 months
Mortality	All-cause mortality	30 days and 6 months
Heart replacement therapies	Composite of long-term LVAD implantation or HTx	30 days and 6 months
Intensive Care Unit	Length of intensive care unit and total hospital stay	through study completion, an average of 6 months

Collaborators and Investigators

• Sponsor: Niguarda Hospital

Publications and helpful links

General Publications

• Garatti L, Frea S, Bocchino PP, Angelini F, Cingolani M, Sacco A, Rondinara GM, Bagnardi V, Sala IM, Kapur NK, Colombo PC, De Ferrari GM, Morici N. Sodium nitroprusside in acute heart failure: A multicenter historic cohort study. Int J Cardiol. 2022 Dec 15;369:37-44. doi: 10.1016/j.ijcard.2022.08.009. Epub 2022 Aug 6.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2021
• Primary Completion (ACTUAL): October 15, 2021
• Study Completion (ACTUAL): November 23, 2021

Study Registration Dates

• First Submitted: August 17, 2021
• First Submitted That Met QC Criteria: August 24, 2021
• First Posted (ACTUAL): August 30, 2021

Study Record Updates

• Last Update Posted (ACTUAL): November 24, 2021
• Last Update Submitted That Met QC Criteria: November 23, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: NTproBNP; Acute Heart Failure; sodium nitroprusside
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Nitric Oxide Donors; Nitroprusside
• Other Study ID Numbers: S_04_06_21_5186

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: not yet decided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No