Goal-directed Afterload Reduction in Acute Congestive Cardiac Decompensation Study (GALACTIC)

This study is currently recruiting participants.
Verified April 2013 by University Hospital, Basel, Switzerland
Sponsor:
Information provided by (Responsible Party):
Christian Müller, MD, University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT00512759
First received: August 6, 2007
Last updated: April 4, 2013
Last verified: April 2013
  Purpose

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


Condition Intervention
Acute Heart Failure
Other: Goal-directed preload and afterload decrement
Drug: Early goal-directed therapy

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Goal-Directed Afterload Reduction in Acute Congestive Cardiac Decompensation Study (GALACTIC)

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • Death or rehospitalization from HF [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • All cause death or rehospitalization [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 700
Study Start Date: September 2007
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 2
Standard treatment of acute HF according to the current guidelines of the ESC
Experimental: 1
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)
Other: Goal-directed preload and afterload decrement
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®), transdermal nitrates (Nitroderm TTS 10®), ACE-inhibitors (Triatec®) and/or ARB (Atacand®).
Other Names:
  • Nitroglycerin Streuli®
  • Nitroderm TTS 10®
  • Triatec®
  • Atacand®
Drug: Early goal-directed therapy
Goal-directed pre- and afterload decrement using Nitroglycerin Streuli®, Nitroderm TTS 10®, Triatec®, Atacand®
Other Names:
  • Goal-directed therapy
  • ADHF therapy
  • Acute heart failure

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00512759

Contacts
Contact: Christian Mueller, MD 0041-61-2655826 chmueller@uhbs.ch

Locations
Brazil
Hospital Sao Paolo Recruiting
Sao Paolo, Brazil, 04024-002
Contact: Mùcio Tavares de Oliveira Jr., Prof.         
Principal Investigator: Mùcio Tavares de Oliveira Jr., Prof.         
Switzerland
Kantonsspital Aarau Recruiting
Aarau, Switzerland, 5001
Contact: Beat Müller, Prof.         
Principal Investigator: Beat Müller, Prof.         
University Hospital Basel Recruiting
Basel, Switzerland, 4031
Contact: Christian Mueller, MD    0041-61-2655826    chmueller@uhbs.ch   
Contact: Christian Mueller, MD         
Principal Investigator: Christian Mueller, Prof.         
Sub-Investigator: Bernadette Meller, MD         
Sub-Investigator: Nisha Arenja, MD         
Sub-Investigator: Raphael Twerenbold, MD         
Sub-Investigator: Tobias Breidthardt, MD         
Sub-Investigator: Mihael Potocki, MD         
Kantonsspital Luzern Recruiting
Luzern, Switzerland, 6000
Contact: Paul Erne, Prof.         
Principal Investigator: Paul Erne, MD         
Kantonsspital St. Gallen Recruiting
St. Gallen, Switzerland, 9007
Contact: Hans Rickli, Prof.         
Principal Investigator: Hans Rickli, Prof.         
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Chritisan Mueller, MD University Hospital, Basel, Switzerland
  More Information

No publications provided

Responsible Party: Christian Müller, MD, Prof. Dr. med., University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT00512759     History of Changes
Other Study ID Numbers: GALACTIC
Study First Received: August 6, 2007
Last Updated: April 4, 2013
Health Authority: Switzerland: Ethikkommission

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Angiotensin-Converting Enzyme Inhibitors
Ramipril
Nitroglycerin
Candesartan cilexetil
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on April 16, 2014