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

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ClinicalTrials.gov Identifier: NCT00512759
Recruitment Status : Active, not recruiting
First Posted : August 8, 2007
Last Update Posted : April 8, 2019
Sponsor:
Information provided by (Responsible Party):
Christian Müller, MD, University Hospital, Basel, Switzerland

Tracking Information
First Submitted Date  ICMJE August 6, 2007
First Posted Date  ICMJE August 8, 2007
Last Update Posted Date April 8, 2019
Actual Study Start Date  ICMJE September 2007
Actual Primary Completion Date February 21, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 24, 2017)
Death or re-hospitalization from HF [ Time Frame: 180 days ]
Death or re-hospitalization due to heart failure at 180 days
Original Primary Outcome Measures  ICMJE
 (submitted: August 7, 2007)
In-hospital days [ Time Frame: 60 days ]
Change History Complete list of historical versions of study NCT00512759 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 24, 2017)
  • All-cause mortality [ Time Frame: 180 days ]
    All-cause mortality at 180 days
  • HF re-hospitalization [ Time Frame: 180 days ]
    Re-hospitalization due to heart failure at 180 days
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Goal-directed Afterload Reduction in Acute Congestive Cardiac Decompensation Study
Official Title  ICMJE Goal-Directed Afterload Reduction in Acute Congestive Cardiac Decompensation Study (GALACTIC)
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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Heart Failure
Intervention  ICMJE Drug: 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®) or nitrospray (Corangin Nitrospray®) transdermal nitrates (Nitroderm TTS 10®), ACE-inhibitors (Triatec®) and/or ARB (Atacand®).
Other Names:
  • Nitroglycerin Streuli®
  • Nitroderm TTS 10®
  • Triatec®
  • Atacand®
  • Corangin Nitrospray®
Study Arms  ICMJE
  • No Intervention: Standard of care
    Standard of care of acute decompensated heart failure will be according to the current guidelines of the European Society of Cardiology (ESC).
  • Experimental: Intervention
    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)
    Intervention: Drug: Goal-directed preload and afterload decrement
Publications * Nyolczas N, Dékány M, Muk B, Szabó 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. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: December 3, 2014)
770
Original Estimated Enrollment  ICMJE
 (submitted: August 7, 2007)
700
Estimated Study Completion Date  ICMJE December 2019
Actual Primary Completion Date February 21, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Bulgaria,   Germany,   Spain,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00512759
Other Study ID Numbers  ICMJE GALACTIC
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Christian Müller, MD, University Hospital, Basel, Switzerland
Study Sponsor  ICMJE University Hospital, Basel, Switzerland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christian Mueller, MD University Hospital, Basel, Switzerland
PRS Account University Hospital, Basel, Switzerland
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP