Goal-directed Afterload Reduction in Acute Congestive Cardiac Decompensation Study

NCT00512759 | Completed Phase 4 DMC

• 1 other identifier: GALACTIC
• Study Type: interventional
• Target: 781
• Locations: 5 countries
• Sites: 12

Brief Summary

The purpose of this study is to determine whether an early goal-directed decrement of preload and afterload with a target systolic blood pressure of 90-110 mmHg by aggressive vasodilatation in patients with acute HF in the non-ICU setting is safe, and leads to a better clinical and economical outcome

Conditions

Acute Heart Failure

Outcome Measures

Primary Outcomes (1)

• Death or re-hospitalization from HF

  Death or re-hospitalization due to heart failure at 180 days

  180 days

Secondary Outcomes (2)

• All-cause mortality

  180 days

• HF re-hospitalization

  180 days

Study Arms (2)

Standard of care

NO INTERVENTION

Standard of care of acute decompensated heart failure will be according to the current guidelines of the European Society of Cardiology (ESC).

Intervention

EXPERIMENTAL

Early goal-directed preload and afterload decrement using a fixed therapy schedule including sublingual or nitrospray and transdermal nitrates together with hydralazine, followed by rapid up-titration of ACE-inhibitors , AT-receptor blockers or neprilysin inhibitors/AT-receptor blockers to achieve maximal vasodilatation with a target systolic blood pressure of 90-110 mmHg. All other elements of treatment will be according to the current guidelines of the European Society of Cardiology (ESC)

Drug: Goal-directed preload and afterload decrement

Interventions

Goal-directed preload and afterload decrement DRUG

Early goal-directed preload and afterload decrement with a target systolic blood pressure (RR) of 90-110 mmHg for the entire hospitalization using sublingual nitrates (Nitroglycerin Streuli®) or nitrospray (Corangin Nitrospray®) transdermal nitrates (Nitroderm TTS 10®), ACE-inhibitors (Triatec®) and/or ARB (Atacand®).

Also known as: Nitroglycerin Streuli®, Nitroderm TTS 10®, Triatec®, Atacand®, Corangin Nitrospray®

Intervention

Eligibility Criteria

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

You may qualify if:

• Acute HF expressed by acute dyspnea New York Heart Association (NYHA) class III or IV, and a BNP-level ≥ 500 pg/ml. The diagnosis of acute HF is additionally based on typical symptoms and clinical findings, supported by appropriate investigations such as ECG, chest X-ray, and Doppler-echocardiography as recommended by current ESC guidelines on the diagnosis and treatment of acute HF

You may not qualify if:

• Cardiopulmonary resuscitation \< 7 days
• Cardiogenic shock, ST-elevation myocardial infarction, or other clinical conditions that require immediate ICU admission or urgent PTCA
• Systolic blood pressure lower than 100 mmHg at presentation
• Primary rhythmogenic cause of acute decompensation (ventricular tachycardia, reentry tachycardia, atrial fibrillation or atrial flutter with a ventricular rate exceeding 140 beats per minute)
• NSTEMI as primary diagnosis
• Severe aortic stenosis
• Adult congenital heart disease as primary cause of acute HF
• Hypertrophic obstructive cardiomyopathy
• Chronic kidney disease with creatinin levels \> 250 µmol/l
• Bilateral renal artery stenosis
• Severe sepsis or other causes of high output failure
• Cirrhosis of the liver CHILD class C
• Previous adverse reactions to nitrates

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (12)

Hospital Sao Paolo

São Paulo, 04024-002, Brazil

Location

5-th Multifunctional Hospital for Active Treatment

Sofia, Bulgaria

Location

National Transport Hospital "Tsar Boris III"

Sofia, Bulgaria

Location

University Hospital "Tsaritsa Joanna-ISUL"

Sofia, Bulgaria

Location

University Hospital Mainz

Mainz, 55131, Germany

Location

Nuremberg Hospital

Nuremberg, 90419, Germany

Location

Hospital Universitari Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

University Hospital Basel

Basel, Canton of Basel-City, 4031, Switzerland

Location

Kantonsspital Aarau

Aarau, 5001, Switzerland

Location

Kantonsspital Luzern

Lucerne, 6000, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Related Publications (3)

• Wussler D, Belkin M, Maeder MT, Walter J, Shrestha S, Kupska K, Stierli M, Flores D, Kozhuharov N, Gualandro DM, de Oliveira Junior MT, Sabti Z, Noveanu M, Socrates T, Bayes-Genis A, Sionis A, Simon P, Michou E, Gujer S, Gori T, Wenzel P, Pfister O, Arenja N, Kobza R, Rickli H, Breidthardt T, Munzel T, Mueller C; GALACTIC Investigators. Comprehensive vasodilatation in women with acute heart failure: Novel insights from the GALACTIC randomized controlled trial. Eur J Heart Fail. 2023 Dec;25(12):2218-2229. doi: 10.1002/ejhf.3065. Epub 2023 Nov 9.

  PMID: 37871997 DERIVED

• Kozhuharov N, Goudev A, Flores D, Maeder MT, Walter J, Shrestha S, Gualandro DM, de Oliveira Junior MT, Sabti Z, Muller B, Noveanu M, Socrates T, Ziller R, Bayes-Genis A, Sionis A, Simon P, Michou E, Gujer S, Gori T, Wenzel P, Pfister O, Conen D, Kapos I, Kobza R, Rickli H, Breidthardt T, Munzel T, Erne P, Mueller C; GALACTIC Investigators; Mueller C, Erne P, Muller B, Rickli H, Maeder M, Tavares de Oliveira M Jr, Munzel T, Bayes-Genis A, Sionis A, Goudev A, Dimov B, Hartwiger S, Arenja N, Glatz B, Herr N, Isenrich R, Mosimann T, Twerenbold R, Boeddinghaus J, Nestelberger T, Puelacher C, Freese M, Vogele J, Meissner K, Martin J, Strebel I, Wussler D, Schumacher C, Osswald S, Vogt F, Hilti J, Barata S, Schneider D, Schwarz J, Fitze B, Hartwiger S, Arenja N, Glatz B, Herr N, Isenrich R, Mosimann T, Twerenbold R, Boeddinghaus J, Nestelberger T, Puelacher C, Freese M, Vogele J, Meissner K, Martin J, Strebel I, Wussler D, Schumacher C, Osswald S, Vogt F, Hilti J, Barata S, Schneider D, Schwarz J, Fitze B, Arenja N, Rentsch K, Bossa A, Jallad S, Soeiro A, Georgiev D, Jansen T, Gebel G, Bossard M, Christ M. Effect of a Strategy of Comprehensive Vasodilation vs Usual Care on Mortality and Heart Failure Rehospitalization Among Patients With Acute Heart Failure: The GALACTIC Randomized Clinical Trial. JAMA. 2019 Dec 17;322(23):2292-2302. doi: 10.1001/jama.2019.18598.

  PMID: 31846016 DERIVED

• Nyolczas N, Dekany M, Muk B, Szabo B. Combination of Hydralazine and Isosorbide-Dinitrate in the Treatment of Patients with Heart Failure with Reduced Ejection Fraction. Adv Exp Med Biol. 2018;1067:31-45. doi: 10.1007/5584_2017_112.

  PMID: 29086392 DERIVED

MeSH Terms

Interventions

Ramipril; candesartan cilexetil

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Christian Mueller, MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: August 6, 2007
• First Posted: August 8, 2007
• Study Start: December 10, 2007
• Primary Completion: August 24, 2018
• Study Completion: February 21, 2019
• Last Updated: November 21, 2019

Record last verified: 2019-11

Locations

BR (1); BU (3); ES (2); DE (2); CH (4)