Growth Hormone in Ischemic Heart Failure
Primary Purpose
Heart Failure, Systolic, Ischemic Heart Disease Chronic
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Somatropin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure, Systolic focused on measuring Heart Failure, Systolic, Ischemic Heart Disease, Growth Hormone Treatment, Insulin Growth Factor I Resistance, Hormone Disturbance
Eligibility Criteria
Inclusion Criteria:
- Ejection fraction at rest less than 40% at the screening visit as measured by echocardiography and a left ventricular enddiastolic diameter > 32 mm/m2
- Stable, optimised therapy for heart failure for at least 4 weeks prior to randomisation including Angiotensin converting enzyme inhibitors, or if not tolerated, angiotensin II blockers and/or digitalis. If tolerated patients should receive beta-blockers for heart failure provided they have had a stable dose for at least 3 months prior to randomisation. The dose of diuretics may vary within a given dose-range considered normal for that patient as determined by the investigator.
- Written informed consent obtained
Exclusion Criteria:
- Uncontrolled hypertension, treated or not treated with a diastolic blood pressure >105 mm Hg
- Haemodynamic clinically significant primary valvular disease or significant congenital heart disease
- Hypertrophic or idiopathic dilated cardiomyopathy
- Acute pericarditis/myocarditis
- Echocardiography findings such as mobile thrombus, significant pericardial effusion and significant left ventricular aneurysm
- Symptomatic or sustained ventricular arrhythmias within the last 3 months not adequately treated with antiarrhythmic drugs or internal cardiovertor defibrillator (ICD)
- Unstable angina pectoris, or myocardial infarction within last 3 months
- percutaneous coronary intervention performed within 6 months prior to randomization
- Planned percutaneous coronary intervention, heart transplantation, other cardiac surgery or other major surgery
- Atrial fibrillation, if a frequency > 100/min or a large frequency variation, according to clinical judgment
- Diabetes mellitus, insulin treated
- Severe liver disease (alanine aminotransferase and/or alanine aminotransferase three times upper limit of normal range laboratory values)
- Severely reduced renal function (S-Creatinine above 250 micromol/l) or suspected significant renal artery stenosis
- Uncontrolled endocrine disorders
- Ongoing treatment with calcium antagonist
- Pregnancy or lactation or females of childbearing potential taking inadequate measures to prevent pregnancy
- History of or ongoing malignant disease
- Previous treatment with growth hormone
- Patients in a catabolic state
- Known drug and/or alcohol abuse
- Inability to cooperate or administer the study drug
- Patients participating in any other clinical study, within 30 days prior to screening visit and/or during this particular study period
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Growth hormon group
Control group
Arm Description
A 12 month study, consisting of a 9 months growth hormone treatment phase followed by a 3 month growth hormone treatment-free period.
A 12 month study, consisting of a 9 month placebo treatment phase followed by a 3 month treatment-free period.
Outcomes
Primary Outcome Measures
Change in left ventricular endsystolic volume
Measured by CMR
Secondary Outcome Measures
Change in enddiastolic volume
Measured by CMR
Change in left ventricular mass
Measured by CMR
Change in left ventricular ejection fraction
Measured by CMR
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04420481
Brief Title
Growth Hormone in Ischemic Heart Failure
Official Title
Growth Hormone Treatment in Patients With Ischemic Heart Failure and Circulating Levels of NT-proBNP
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
April 28, 2004 (Actual)
Primary Completion Date
February 25, 2012 (Actual)
Study Completion Date
February 25, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Göteborg University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
In a double-blind, placebo-controlled trial, we randomly assigned 37 patients (mean age 66 years; 95% male) with ischemic heart failure (HF) (ejection fraction (EF) < 40%) to a 9-month treatment with either recombinant human GH (1.4 mg every other day) or placebo, with subsequent 3-month treatment-free follow-up. The primary outcome was change in left ventricular (LV) end-systolic volume measured by cardiac magnetic resonance (CMR). Secondary outcomes comprised changes in cardiac structure and EF. Prespecified tertiary outcomes included changes in New York Heat Association (NYHA) functional class and quality of life (QoL), as well as levels of insulin-like growth factor-1 (IGF-1) and N-terminal pro-brain natriuretic peptide (NT-proBNP).
Detailed Description
TITLE: GROWTH HORMONE IN HEART FAILURE Addition of recombinant human growth hormone to standard heart failure therapy in patients with congestive heart failure due to ischaemic heart disease.
A 12 month study, consisting of a 9 month double-blind, placebo-controlled randomised growth hormone treatment phase followed by a 3 month growth hormone treatment-free period.
STUDY PHASE: III
COORDINATING CENTRE:
Endocrine Cardiac Unit (ECU) Sahlgrenska University Hospital, Sahlgrenska S-413 45 Göteborg Sweden
STUDY PRODUCT:
Somatropin, recombinant human growth hormone (rhGH), Saizen® 8 mg (24 IE).
CONTROL PRODUCT:
Placebo for Saizen®
DOSAGE OF STUDY PRODUCT:
1,4 mg (4,2 IE) every other day.
DOSAGE:
9 month treatment period and a 3 month follow-up period. ROUTE OF ADMINISTRATION One subcutaneous injection of Saizen® of study product, or corresponding placebo in the thigh or abdomen given in the evening given every other day.
STUDY DESIGN:
Double-blind (regarding treatment), parallel, placebo-controlled, randomised.
STUDY POPULATION:
Female and male patients 75 years of age or below with congestive heart failure (NYHA class II or III) due to ischemic heart disease.
NUMBER OF PATIENTs:
54 evaluable patients. MULTICENTRE: Yes. NUMBER OF CENTRES: Four
ALLOCATION OF TREATMENT:
Randomisation to treatment if all inclusion/exclusion criteria are met.
PRIMARY OBJECTIVE:
To investigate the effect of subcutaneously administered Saizen® compared with placebo on left ventricular endsystolic volume by MRI in patients with congestive heart failure due to ischaemic heart disease.
SECONDARY OBJECTIVE:
To determine the effect of Saizen® on enddiastolic volume, left ventricular mass and left ventricular ejection fraction
TERTIARY OBJECTIVES:
To determine the effect of Saizen® on change in NYHA class after 9 months of follow up.
To determine the effect of Saizen® on circulating levels of IGF-I and IGFBP-3 and to evaluate the correlation between changes in IGF-I and the respective changes in left ventricular ejection fraction, wall stress and left ventricular mass.
To evaluate the effect of Saizen® on quality of life by using two different questionnaires (Minnesota - Living with Heart Failure and Cardiac Health Profile).
To determine the effect of Saizen® on neurohormonal activation by measuring NT-proBNP
SAFETY VARIABLES:
Hospitalization, morbidity and mortality.
Clinical events, including tendency to fluid retention, glucose intolerance, arrhythmias and worsening heart failure.
Electrolytes, haematology, prothrombin complex, parameters for renal and hepatic function.
ADVERSE EVENTS:
Spontaneously reported from patients and asked for. To be recorded in Case Report Forms (CRFs) and on separate Adverse Event form if serious Adverse Event.
STATISTICS AND DATABASE MANAGEMENT:
Data management will be performed by Scandinavian Contract Research Institute and when clean file is declared data will be made available to the statistician for the analysis. The analysis will be performed according to the intention to treat principle.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Systolic, Ischemic Heart Disease Chronic
Keywords
Heart Failure, Systolic, Ischemic Heart Disease, Growth Hormone Treatment, Insulin Growth Factor I Resistance, Hormone Disturbance
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
A 12 month study, consisting of a 9 months' double-blind, placebo-controlled randomised growth hormone treatment phase followed by a 3 months' growth hormone treatment-free period.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
All care providers and patients were masked with respect to the study drug during the study
Allocation
Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Growth hormon group
Arm Type
Active Comparator
Arm Description
A 12 month study, consisting of a 9 months growth hormone treatment phase followed by a 3 month growth hormone treatment-free period.
Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
A 12 month study, consisting of a 9 month placebo treatment phase followed by a 3 month treatment-free period.
Intervention Type
Drug
Intervention Name(s)
Somatropin
Intervention Description
Dose: 1,4 mg (4,2 IE) every other day Dosage: 9 month treatment period and a 3 month follow-up period Administration: One subcutaneous injection of somatropin or corresponding placebo in the thigh or abdomen given in the evening given every other day.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Change in left ventricular endsystolic volume
Description
Measured by CMR
Time Frame
9 months
Secondary Outcome Measure Information:
Title
Change in enddiastolic volume
Description
Measured by CMR
Time Frame
9 months
Title
Change in left ventricular mass
Description
Measured by CMR
Time Frame
9 months
Title
Change in left ventricular ejection fraction
Description
Measured by CMR
Time Frame
9 months
Other Pre-specified Outcome Measures:
Title
Change in QoL Questionnaire
Time Frame
9 months
Title
Change in NT-proBNP level
Description
blood sample
Time Frame
9 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Ejection fraction at rest less than 40% at the screening visit as measured by echocardiography and a left ventricular enddiastolic diameter > 32 mm/m2
Stable, optimised therapy for heart failure for at least 4 weeks prior to randomisation including Angiotensin converting enzyme inhibitors, or if not tolerated, angiotensin II blockers and/or digitalis. If tolerated patients should receive beta-blockers for heart failure provided they have had a stable dose for at least 3 months prior to randomisation. The dose of diuretics may vary within a given dose-range considered normal for that patient as determined by the investigator.
Written informed consent obtained
Exclusion Criteria:
Uncontrolled hypertension, treated or not treated with a diastolic blood pressure >105 mm Hg
Haemodynamic clinically significant primary valvular disease or significant congenital heart disease
Hypertrophic or idiopathic dilated cardiomyopathy
Acute pericarditis/myocarditis
Echocardiography findings such as mobile thrombus, significant pericardial effusion and significant left ventricular aneurysm
Symptomatic or sustained ventricular arrhythmias within the last 3 months not adequately treated with antiarrhythmic drugs or internal cardiovertor defibrillator (ICD)
Unstable angina pectoris, or myocardial infarction within last 3 months
percutaneous coronary intervention performed within 6 months prior to randomization
Planned percutaneous coronary intervention, heart transplantation, other cardiac surgery or other major surgery
Atrial fibrillation, if a frequency > 100/min or a large frequency variation, according to clinical judgment
Diabetes mellitus, insulin treated
Severe liver disease (alanine aminotransferase and/or alanine aminotransferase three times upper limit of normal range laboratory values)
Severely reduced renal function (S-Creatinine above 250 micromol/l) or suspected significant renal artery stenosis
Uncontrolled endocrine disorders
Ongoing treatment with calcium antagonist
Pregnancy or lactation or females of childbearing potential taking inadequate measures to prevent pregnancy
History of or ongoing malignant disease
Previous treatment with growth hormone
Patients in a catabolic state
Known drug and/or alcohol abuse
Inability to cooperate or administer the study drug
Patients participating in any other clinical study, within 30 days prior to screening visit and/or during this particular study period
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data will be share upon reasonable request
IPD Sharing Time Frame
3 months
IPD Sharing Access Criteria
A researcher that can show previous scientific merits that can be validated
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Growth Hormone in Ischemic Heart Failure
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