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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00391846

Enrollment

252

Registered

2006-10-25

Start date

2006-10-31

Completion date

2009-01-31

Last updated

2012-06-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart Failure, Ventricular Dysfunction, Left

Keywords

Heart Failure, Ventricular Dysfunction, NTproBNP

Brief summary

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

Interventions

DRUGCaptopril

DRUGEnalapril

DRUGLisinopril

DRUGRamipril

DRUGTrandolapril

DRUGBisoprolol

DRUGCarvedilol

DRUGMetoprolol succinate

DRUGCandesartan

DRUGValsartan

DRUGEplerenone

DRUGSpironolactone

DRUGDiuretics

DRUGHF treatment according to Swedish guidelines

PROCEDUREBlood samples

PROCEDUREThe Kansas City Cardiomyopathy Questionnaire (KCCQ)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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)	9 months	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

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

Countries

Sweden

Participant flow

Recruitment details

This was a randomised, parallel group, single blind, multicentre, 9-month study in chronic heart failure in patients with New York Heart Association classification of heart failure (NYHA) class II-IV, left ventricular systolic dysfunction and elevated NT-proBNP levels in the primary care setting.

Pre-assignment details

At visit 1 was the NT-proBNP value measured at this value should be above 800 (females) or 1000 (males) before randomisation at visit 2. One patient from each group are excluded from the full analysis set (FAS) due to total unavailability of efficacy data after randomisation.

Participants by arm

Arm	Count
Guided by NT-proBNP Chronic heart failure treatment guided by clinical symptoms, signs and NT-proBNP	127
Not Guided by NT-proBNP Chronic heart failure treatment guided by clinical symptoms and signs	125
Total	252

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	4	1
Overall Study	Developed study specific DC criteria	0	1
Overall Study	Did not meet the required elig. crit	2	2
Overall Study	Withdrawal by Subject	2	3

Baseline characteristics

Characteristic	Guided by NT-proBNP	Not Guided by NT-proBNP	Total
Age Continuous	78 Years	77 Years	77 Years
Diastolic blood pressure	73 mmHg STANDARD_DEVIATION 11	75 mmHg STANDARD_DEVIATION 12	74 mmHg STANDARD_DEVIATION 11
Electrocardiogram (ECG), Abnormal/Normal Abnormal ECG	115 Participants	113 Participants	228 Participants
Electrocardiogram (ECG), Abnormal/Normal Normal ECG	12 Participants	12 Participants	24 Participants
Pulse	71 Beats/minute STANDARD_DEVIATION 14	72 Beats/minute STANDARD_DEVIATION 14	72 Beats/minute STANDARD_DEVIATION 14
Sex: Female, Male Female	30 Participants	42 Participants	72 Participants
Sex: Female, Male Male	97 Participants	83 Participants	180 Participants
Systolic blood pressure	133 mmHg STANDARD_DEVIATION 21	135 mmHg STANDARD_DEVIATION 22	134 mmHg STANDARD_DEVIATION 21

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 127	0 / 125
serious Total, serious adverse events	46 / 127	41 / 125

Outcome results

Primary

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

Time frame: 9 months