Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Evaluation of Heart Failure Treatment Guided by N-terminal Pro B-type Natriuretic Peptide (NTproBNP) vs Clinical Symptoms and Signs Alone

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00391846
First received: October 19, 2006
Last updated: June 18, 2012
Last verified: June 2012
  Purpose

The purpose is to study if HF treatment guided by NTproBNP in addition to clinical symptoms and signs is more effective than treatment guided by clinical symptoms and signs alone in patients with HF and left ventricular systolic dysfunction


Condition Intervention Phase
Heart Failure
Ventricular Dysfunction, Left
Drug: Captopril
Drug: Enalapril
Drug: Lisinopril
Drug: Ramipril
Drug: Trandolapril
Drug: Bisoprolol
Drug: Carvedilol
Drug: Metoprolol succinate
Drug: Candesartan
Drug: Valsartan
Drug: Eplerenone
Drug: Spironolactone
Drug: Diuretics
Drug: HF treatment according to Swedish guidelines
Procedure: Blood samples
Procedure: The Kansas City Cardiomyopathy Questionnaire (KCCQ)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Randomised, Single Blind, Multicentre, 9-month, Phase IV Study, Comparing Treatment Guided by Clinical Symptoms and Signs and NT-proBNP vs Treatment Guided by Clinical Symptoms and Signs Alone, in Patients With Heart Failure (HF) and Left Ventricular Systolic Dysfunction

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Composite Value of 3 Variables After 9 Months: Cardiovascular Death (Days Alive), Cardiovascular Hospitalization (Days Out of Hospital), Heart Failure Symptoms (Symptom Score Subset of the Kansas City Cardiomyopathy Questionnaire - Questions 3,5,7,9) [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    The non-parametric scale is constructed from 3 variables, modified after Cleland. Each patient receives a rank score from 1 to 246 (246-number of patients in the study). The lowest score receive patients who die (due to CV event), next patients still alive at end-of-study with the worst composite score, the best alive patients with 0 days in hospital and the largest improvement in the KCCQ (self-administered by patient symptom score, where the higher score reflect better health status). Scores will be summarized using non-parametric calculations. The mean of non-parametric scores is presented


Secondary Outcome Measures:
  • Number of CV Deaths [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Number of deaths

  • Number of Days in Hospital for CV Reason [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Each overnight stay is counted as one day. The lower the better

  • Changes in Heart Failure Symptoms [ Time Frame: 9 months and baseline ] [ Designated as safety issue: No ]
    Changes from baseline in the symptom score subset (question 3, 5, 7 and 9) of KCCQ (swelling, fatigue, shortness of breath, shortness of breath night time). KCCQ is a self-administered by patient symptom score, where higher score reflect better health status. Scale scores are transformed to a 0 to 100 range by subtracting the lowest possible scale score, dividing by the range of the scale and multiplying by 100. This mean that the KCCQ scale is from 0 to 100 with the higher value showing a better health status.

  • Changes in NT-proBNP Values Over Time in All Patients [ Time Frame: 9 months and baseline ] [ Designated as safety issue: No ]
    The 95% confidential interval (CI) is given as measure of dispersion

  • Changes in Health-related Quality of Life [ Time Frame: 9 months and baseline ] [ Designated as safety issue: No ]
    Change range -100 to 100. The higher the better.

  • Total Number of Titration Steps in Prescribed Heart Failure Treatment [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Each titration step in prescribed medication is counted as one step, either up or down. One step up indicates an increase of dose in prescribed medication and one step down indicates a decrease of dose in prescribed medication. The sum of steps is given as a score. Score is given for each arm as a total number of titration steps for all patients in arm.

  • Discontinuations [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    Number of patients discontinued due to adverse events'


Enrollment: 252
Study Start Date: October 2006
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Guided by NT-proBNP
Treatment guided by clinical symptoms and signs + NTproBNP
Drug: Captopril Drug: Enalapril Drug: Lisinopril Drug: Ramipril Drug: Trandolapril Drug: Bisoprolol Drug: Carvedilol Drug: Metoprolol succinate Drug: Candesartan
Other Name: Atacand
Drug: Valsartan Drug: Eplerenone Drug: Spironolactone Drug: Diuretics Drug: HF treatment according to Swedish guidelines Procedure: Blood samples Procedure: The Kansas City Cardiomyopathy Questionnaire (KCCQ)
Not Guided by NT-proBNP
Treatment guided by clinical symptoms and signs
Drug: Captopril Drug: Enalapril Drug: Lisinopril Drug: Ramipril Drug: Trandolapril Drug: Bisoprolol Drug: Carvedilol Drug: Metoprolol succinate Drug: Candesartan
Other Name: Atacand
Drug: Valsartan Drug: Eplerenone Drug: Spironolactone Drug: Diuretics Drug: HF treatment according to Swedish guidelines Procedure: Blood samples Procedure: The Kansas City Cardiomyopathy Questionnaire (KCCQ)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female/male, over 18 years with previously verified HF with left ventricular systolic dysfunction.
  • New York Heart Association(NYHA) class II-IV,
  • NTproBNP males>800 ng/L, females >1000 ng/L

Exclusion Criteria:

  • Planned CV hospitalisation, stroke or acute myocardial infarction (MI) last 3 months,
  • Mitral/aortic stenosis,
  • Patients already receiving optimal HF treatment,
  • Severe reduction of kidney function
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00391846

Locations
Sweden
Research Site
Alvesta, Sweden
Research Site
Arvika, Sweden
Research Site
Bjuv, Sweden
Research Site
Borensberg, Sweden
Research Site
Bromma, Sweden
Research Site
Dalby, Sweden
Research Site
Eskilstuna, Sweden
Research Site
Gagnef, Sweden
Research Site
Goeteborg, Sweden
Research Site
Hisings Karra, Sweden
Research Site
Huddinge, Sweden
Research Site
Huskvarna, Sweden
Research Site
Joenkoeping, Sweden
Research Site
Kalmar, Sweden
Research Site
Kungalv, Sweden
Research Site
Lerum, Sweden
Research Site
Lessebo, Sweden
Research Site
Lidkoping, Sweden
Research Site
Lilla Edet, Sweden
Research Site
Linkoeping, Sweden
Research Site
Ludvika, Sweden
Research Site
Lyckeby, Sweden
Research Site
Malmo, Sweden
Research Site
Moheda, Sweden
Research Site
Motala, Sweden
Research Site
Orebro, Sweden
Research Site
Ostersund, Sweden
Research Site
Skanor, Sweden
Research Site
Soderakra, Sweden
Research Site
Stenungsund, Sweden
Research Site
Stocksund, Sweden
Research Site
Timra, Sweden
Research Site
Uddevalla, Sweden
Research Site
Ulricehamn, Sweden
Research Site
Umea, Sweden
Research Site
Uppsala, Sweden
Research Site
Vasteras, Sweden
Research Site
Vastervik, Sweden
Research Site
Vaxjo, Sweden
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: AstraZeneca Sweden Medical Director, MD AstraZeneca
Principal Investigator: Hans Persson, MD, PhD Danderyd Hospital, Sweden
Study Director: Bjorn Eriksson, MD AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00391846     History of Changes
Other Study ID Numbers: D2452L00010, EUDRACT No. 2006-001259-36, SIGNAL HF
Study First Received: October 19, 2006
Results First Received: May 10, 2010
Last Updated: June 18, 2012
Health Authority: Sweden: Medical Products Agency

Keywords provided by AstraZeneca:
Heart Failure
Ventricular Dysfunction
NTproBNP

Additional relevant MeSH terms:
Heart Failure
Signs and Symptoms
Ventricular Dysfunction
Ventricular Dysfunction, Left
Cardiovascular Diseases
Heart Diseases
Metoprolol
Metoprolol succinate
Spironolactone
Trandolapril
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Angiotensin-Converting Enzyme Inhibitors
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents
Cardiovascular Agents
Diuretics
Diuretics, Potassium Sparing
Enzyme Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Mineralocorticoid Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 25, 2014