Goal-directed Afterload Reduction in Acute Congestive Cardiac Decompensation Study

Condition(s) targeted: Acute Heart Failure

Intervention: Goal-directed preload and afterload decrement (Other); Early goal-directed therapy (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: University Hospital, Basel, Switzerland

Official(s) and/or principal investigator(s):
Christian Mueller, MD, Principal Investigator, Affiliation: University Hospital, Basel, Switzerland

Overall contact:
Christian Mueller, MD, Phone: 0041-61-2655826, Email: chmueller@uhbs.ch

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

Official title: Goal-Directed Afterload Reduction in Acute Congestive Cardiac Decompensation Study (GALACTIC)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Death or rehospitalization from HF

Secondary outcome: All cause death or rehospitalization

Detailed description: Background: Heart failure (HF) is a chronic and progressive illness resulting from a variety of cardiac causes, including ischemic and valvular heart disease, dilatative cardiomyopathy or hypertension. HF may also develop suddenly, particularly as a complication of acute myocardial infarction or as an acute exacerbation in patients with previously compensated chronic HF. Acute HF requires immediate treatment that centers on reducing myocardial oxygen demand and augmenting forward blood flow by removal of excess fluid with diuretics and reduction of preload and afterload with vasodilatators. The aging of our population and the higher number of patients surviving acute myocardial infarctions have lead to a dramatic increase in the incidence and prevalence of HF, and obviously also on total cost burden of the disease. For multiple reasons including need for restrictive use of the limited number of ICU hospital beds the vast majority of elderly patients with acute HF are treated in a non-ICU setting. Unfortunately, the optimal treatment of acute HF in the non-ICU setting is not well defined. Pathophysiological considerations and preliminary data from the ICU setting suggest that aggressive venous and arterial vasodilation may improve short and long-term outcome. Aim: To test the hypotheses that: • 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 Methods: Design: Prospective, randomized, controlled, open label, interventional study Setting: University Hospital Basel Patients: Patients with acute HF not requiring ICU admission Patients admitted to the emergency department with acute HF will be randomized to:

- Early goal-directed preload and afterload decrement using a fixed therapy schedule

including sublingual and transdermal nitrates, and hydralazine, followed by rapid up-titration of ACE-inhibitors or 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)

- Standard treatment of acute HF according to the current guidelines of the ESC.

Clinical Significance: Despite the clinical and economical importance of acute HF, the optimal treatment of acute HF is ill-defined. We strongly believe that our novel therapeutic strategy will significantly reduce morbidity, length of hospitalisation, and possibly mortality of affected patients. This would represent a first major step for an evidence-based management of this common condition. Documenting medical and economic benefit of a simple, safe, and inexpensive medical therapy in a randomised controlled clinical trial would provide evidence-based care for the majority of patients presenting with acute HF worldwide. All drugs applied in our strategy are off-patent and therefore relatively low-cost. Successful implication of our treatment algorithm has the potential to significantly reduce treatment costs.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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 Exclusion Criteria:

- 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

Christian Mueller, MD, Phone: 0041-61-2655826, Email: chmueller@uhbs.ch

Hospital Sao Paolo, Sao Paolo 04024-002, Brazil; Recruiting
Mùcio Tavares de Oliveira Jr., Prof.
Mùcio Tavares de Oliveira Jr., Prof., Principal Investigator

University Hospital Mainz, Mainz 55131, Germany; Recruiting
Thomas Muenzel, Prof.
Thomas Muenzel, Prof., Principal Investigator

Nuremberg Hospital, Nuremberg 90419, Germany; Not yet recruiting
Michael Christ, Prof.
Michael Christ, Prof., Principal Investigator

Kantonsspital Aarau, Aarau 5001, Switzerland; Completed

University Hospital Basel, Basel 4031, Switzerland; Recruiting
Christian Mueller, MD, Phone: 0041-61-2655826, Email: chmueller@uhbs.ch
Raphael Twerenbold, MD
Christian Mueller, Prof., Principal Investigator
Raphael Twerenbold, MD, Sub-Investigator
Tobias Breidthardt, MD, Sub-Investigator
Zoraida Moreno, MD, Sub-Investigator
Carmela Schumacher, MSc, Sub-Investigator
Kateryna Pershyna, MD, Sub-Investigator

Kantonsspital Luzern, Luzern 6000, Switzerland; Completed

Kantonsspital St. Gallen, St. Gallen 9007, Switzerland; Recruiting
Hans Rickli, Prof.
Hans Rickli, Prof., Principal Investigator

Starting date: September 2007
Last updated: July 8, 2015