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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Heart Failure, Ventricular Dysfunction, Left

Intervention / Treatment
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* 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)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Guided by NT-proBNP<br>Treatment guided by clinical symptoms and signs + NTproBNP | Drug: Captopril<br> <br> Drug: Enalapril<br> <br> Drug: Lisinopril<br> <br> Drug: Ramipril<br> <br> Drug: Trandolapril<br> <br> Drug: Bisoprolol<br> <br> Drug: Carvedilol<br> <br> Drug: Metoprolol succinate<br> <br> Drug: Candesartan<br> <br> * Other names: Atacand;Drug: Valsartan<br> <br> Drug: Eplerenone<br> <br> Drug: Spironolactone<br> <br> Drug: Diuretics<br> <br> Drug: HF treatment according to Swedish guidelines<br> <br> Procedure: Blood samples<br> <br> Procedure: The Kansas City Cardiomyopathy Questionnaire (KCCQ)<br> <br> |
| Other: Not Guided by NT-proBNP<br>Treatment guided by clinical symptoms and signs | Drug: Captopril<br> <br> Drug: Enalapril<br> <br> Drug: Lisinopril<br> <br> Drug: Ramipril<br> <br> Drug: Trandolapril<br> <br> Drug: Bisoprolol<br> <br> Drug: Carvedilol<br> <br> Drug: Metoprolol succinate<br> <br> Drug: Candesartan<br> <br> * Other names: Atacand;Drug: Valsartan<br> <br> Drug: Eplerenone<br> <br> Drug: Spironolactone<br> <br> Drug: Diuretics<br> <br> Drug: HF treatment according to Swedish guidelines<br> <br> Procedure: Blood samples<br> <br> Procedure: The Kansas City Cardiomyopathy Questionnaire (KCCQ)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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 | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of CV Deaths | Number of deaths | 9 months | 
| Number of Days in Hospital for CV Reason | Each overnight stay is counted as one day. The lower the better | 9 months | 
| Changes in Heart Failure Symptoms | 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. | 9 months and baseline | 
| Changes in NT-proBNP Values Over Time in All Patients | The 95% confidential interval (CI) is given as measure of dispersion | 9 months and baseline | 
| Changes in Health-related Quality of Life | Change range -100 to 100. The higher the better. | 9 months and baseline | 
| Total Number of Titration Steps in Prescribed Heart Failure Treatment | 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. | 9 months | 
| Discontinuations | Number of patients discontinued due to adverse events' | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Ventricular Dysfunction, NTproBNP