Ignite Creation Date:
2024-05-05 @ 11:21 AM
Last Modification Date:
2024-10-26 @ 9:01 AM
Study NCT ID:
NCT00000516
Status:
COMPLETED
Last Update Posted:
2016-04-15
First Post:
1999-10-27
Brief Title:
Studies of Left Ventricular Dysfunction SOLVD
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2012-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To determine if enalapril treatment of left ventricular dysfunction LVD due to ischemic or hypertensive heart disease led to reduced mortality and morbidity in symptomatic and asymptomatic patients There were a Prevention Trial a Treatment Trial and a registry
Detailed Description:
BACKGROUND
Approximately two million Americans suffer from heart failure Since the prevalence of congestive heart failure is known to increase with age improvements in the average life expectancy would be expected to increase the magnitude of the problem over the next few decades While advances in the treatment of hypertension coronary artery disease and surgical treatment of congenital and valvular heart disease have prolonged survival many of these patients ultimately develop heart failure in later life
The therapy of congestive heart failure has undergone rapid change Until the early 1970s the mainstay of therapy for the patient with acute and chronic congestive heart failure was digitalis and diuretics The use of digitalis in patients with heart failure secondary to ischemic heart disease and in those with severe left ventricular failure of either nonischemic or ischemic origin was however controversial
Controversy over the acute and long-term effects of digitalis led to the introduction of a variety of alternative and supplemental therapeutic approaches for the patient with heart failure In the mid 1980s a wide spectrum of vasodilators was available New at that time inotropic agents also found applications as alternatives or supplements to digitalis administration Although all of these drugs had been shown to be of some benefit in the management of patients with chronic heart failure there was inadequate information as to the long-term hemodynamic effects of some of these agents and practically no information regarding their effect on survival
The recognition that patients with congestive heart failure often have elevated peripheral vascular resistance led to the introduction of vasodilator therapy Of the vasodilators the angiotensin-converting enzyme ACE inhibitors appeared to be the most promising because they had been shown to counteract some of the major adverse hormonal and vasoconstrictor mechanisms relieve symptoms diminish cardiac dilatation after myocardial infarction and improve exercise capacity and ejection fraction
SOLVD was initiated in 1986 primarily to evaluate the effects of enalapril an angiotensin-converting enzyme ACE inhibitor Two considerations influenced the design of SOLVD it was possible that drug treatment given to patients who already had manifest congestive heart failure might not be as beneficial as initiating treatment in asymptomatic left ventricular dysfunction patients early treatment of such asymptomatic patients might be less beneficial as the patient might not have measurable activation of the renin-angiotensin axis
The Request for Proposals was released in August 1984 with the first awards made in July 1985 A second Request for Proposals for additional clinical centers was released in March 1985
DESIGN NARRATIVE
Both trials were randomized and double-blind Prior to randomization all patients received enalapril and placebo for two weeks to enable early detection of non-compliant patients those unable to tolerate the drug and those with early side-effects After completion of the pre-randomization period participants were allocated to enalapril or placebo using a permuted block randomization within each of the clinical centers Follow-up visits were scheduled for two and six weeks after randomization and then at four eight and twelve months Thereafter clinic visits were scheduled at four-month intervals Patients were followed for a minimum of two years and a maximum of five years Primary outcome for each trial was all-cause mortality Secondary endpoints included cardiovascular mortality sudden death due to worsening congestive heart failure hospitalization for congestive heart failure myocardial infarction stroke need for cardiac transplantation and quality of life Onset of congestive heart failure was an additional outcome in the Prevention Trial Seven substudies were conducted among subsets of participants and included diastolic function echocardiography exercise neurohumoral quality of life radionuclide sudden death Patient recruitment began in July 1986 Recruitment in the Treatment Trial ended six months ahead of schedule in February 1989 and follow-up ended in February 1991 The Prevention Trial ended recruitment in April 1990 and completed follow-up in July 1991 Data analysis continued through November 1994
The trial also included a registry which enrolled 6300 patients to study the influence of a number of patient characteristics on mortality Eighteen of the clinical centers participated Data were collected from consecutive patients with ejection fraction less than 45 or with radiologic evidence of congestive heart failure over a twelve month period At one year patients vital status was ascertained by mail and if necessary by telephone follow-up One year follow-up was completed on all registry patients by May 1990 Longer term follow-up was done through the National Death Index
Approximately two million Americans suffer from heart failure Since the prevalence of congestive heart failure is known to increase with age improvements in the average life expectancy would be expected to increase the magnitude of the problem over the next few decades While advances in the treatment of hypertension coronary artery disease and surgical treatment of congenital and valvular heart disease have prolonged survival many of these patients ultimately develop heart failure in later life
The therapy of congestive heart failure has undergone rapid change Until the early 1970s the mainstay of therapy for the patient with acute and chronic congestive heart failure was digitalis and diuretics The use of digitalis in patients with heart failure secondary to ischemic heart disease and in those with severe left ventricular failure of either nonischemic or ischemic origin was however controversial
Controversy over the acute and long-term effects of digitalis led to the introduction of a variety of alternative and supplemental therapeutic approaches for the patient with heart failure In the mid 1980s a wide spectrum of vasodilators was available New at that time inotropic agents also found applications as alternatives or supplements to digitalis administration Although all of these drugs had been shown to be of some benefit in the management of patients with chronic heart failure there was inadequate information as to the long-term hemodynamic effects of some of these agents and practically no information regarding their effect on survival
The recognition that patients with congestive heart failure often have elevated peripheral vascular resistance led to the introduction of vasodilator therapy Of the vasodilators the angiotensin-converting enzyme ACE inhibitors appeared to be the most promising because they had been shown to counteract some of the major adverse hormonal and vasoconstrictor mechanisms relieve symptoms diminish cardiac dilatation after myocardial infarction and improve exercise capacity and ejection fraction
SOLVD was initiated in 1986 primarily to evaluate the effects of enalapril an angiotensin-converting enzyme ACE inhibitor Two considerations influenced the design of SOLVD it was possible that drug treatment given to patients who already had manifest congestive heart failure might not be as beneficial as initiating treatment in asymptomatic left ventricular dysfunction patients early treatment of such asymptomatic patients might be less beneficial as the patient might not have measurable activation of the renin-angiotensin axis
The Request for Proposals was released in August 1984 with the first awards made in July 1985 A second Request for Proposals for additional clinical centers was released in March 1985
DESIGN NARRATIVE
Both trials were randomized and double-blind Prior to randomization all patients received enalapril and placebo for two weeks to enable early detection of non-compliant patients those unable to tolerate the drug and those with early side-effects After completion of the pre-randomization period participants were allocated to enalapril or placebo using a permuted block randomization within each of the clinical centers Follow-up visits were scheduled for two and six weeks after randomization and then at four eight and twelve months Thereafter clinic visits were scheduled at four-month intervals Patients were followed for a minimum of two years and a maximum of five years Primary outcome for each trial was all-cause mortality Secondary endpoints included cardiovascular mortality sudden death due to worsening congestive heart failure hospitalization for congestive heart failure myocardial infarction stroke need for cardiac transplantation and quality of life Onset of congestive heart failure was an additional outcome in the Prevention Trial Seven substudies were conducted among subsets of participants and included diastolic function echocardiography exercise neurohumoral quality of life radionuclide sudden death Patient recruitment began in July 1986 Recruitment in the Treatment Trial ended six months ahead of schedule in February 1989 and follow-up ended in February 1991 The Prevention Trial ended recruitment in April 1990 and completed follow-up in July 1991 Data analysis continued through November 1994
The trial also included a registry which enrolled 6300 patients to study the influence of a number of patient characteristics on mortality Eighteen of the clinical centers participated Data were collected from consecutive patients with ejection fraction less than 45 or with radiologic evidence of congestive heart failure over a twelve month period At one year patients vital status was ascertained by mail and if necessary by telephone follow-up One year follow-up was completed on all registry patients by May 1990 Longer term follow-up was done through the National Death Index
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: