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| ID | Type | Description | Link |
|---|---|---|---|
| Grant Number UL1 RR024989 | Other Grant/Funding Number | CWRU-CTSC | |
| ULI RR024989 | Other Grant/Funding Number | NIH/NCRR CWRU-CTSC |
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| Name | Class |
|---|---|
| National Center for Research Resources (NCRR) | NIH |
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Sildenafil (Viagra) is known to reduce pulmonary hypertension. Heart failure patients also have pulmonary hypertension and several recent reports have shown that sildenafil leads to an improvement in their exercise capacity. In these studies sildenafil caused a reduction in the pulmonary and systemic vascular resistances, improved pulmonary gas diffusion and perhaps increased cardiac output. It is uncertain if left ventricular filling pressures are reduced and whether there is improvement in left ventricular relaxation. The investigators hypothesize that in heart failure patients the improvement in exercise capacity associated with sildenafil is related to a significant reduction in left ventricular filling pressures. The investigators propose to study 20 patients with stable but moderately symptomatic heart failure. The study design is a randomized cross-over trial of the administration of a single dose of sildenafil 50 mg or a matching placebo. Exercise capacity will be determined before and after the oral administration of sildenafil 50 mg or placebo. Left ventricular filling pressures will be assessed by Doppler echocardiography and the serum level of B-type natriuretic peptide (BNP is known to increase with higher left ventricular filling pressures). After an initial echocardiogram and performing a 6 minute walk test, the patient will then be given either sildenafil or a matching placebo in a randomized double-blind fashion. One hr later a blood sample for serum BNP, the echocardiogram and the 6 minute walk test will be repeated.
Sildenafil (Viagra) has been extensively studied in patients with idiopathic pulmonary hypertension. It reduces pulmonary vascular resistance, improves exercise capacity and is now an approved therapy for this condition. Heart failure (HF) patients also have pulmonary hypertension and several recent reports have shown that sildenafil leads to an improvement in their exercise capacity. In HF sildenafil causes a reduction in the pulmonary and systemic vascular resistances, improves pulmonary gas diffusion and perhaps increases cardiac output. It is uncertain if left ventricular filling pressures are reduced and whether there is improvement in left ventricular relaxation. We hypothesize that in HF patients the improvement in exercise capacity associated with sildenafil is related to a significant reduction in left ventricular filling pressures. We propose to study 10 patients with stable, symptomatic HF Class III. The study design is a randomized cross-over assignment of the administration of a single oral dose of sildenafil 50 mg or a matching placebo. Patients will be excluded if walking is impaired due to non-cardiac conditions or if they are taking nitrates. Exercise capacity will be determined before and 60 minutes after the oral administration of sildenafil 50 mg or placebo. The difference in the standardized 6 minute walk test (distance patient is able to walk over a 6 minute interval) will be used to assess exercise capacity. Left ventricular filling pressures will be assessed by Doppler echocardiography and the serum level of B-type natriuretic peptide (BNP). Evaluation of left ventricular relaxation will be determined by Doppler echocardiography techniques. Each patient will have a blood sample for BNP, an initial echocardiogram and perform a 6 minute walk test. They will then be given a single dose of either sildenafil or a matching placebo in a randomized double-blind fashion. The randomization was performed so that half of the group would receive the placebo on the initial test and sildenafil on the subsequent test and the other half would have the reverse sequence. One hr after the medication/placebo administration a blood sample for serum BNP, the echocardiogram and the 6 minute walk test will be repeated. After completion of the above protocol, the patient will return in 48 hrs and the protocol will be repeated with the predetermined assignment of either placebo or sildenafil.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| sildenafil | Experimental | Effect of oral administration of a single dose of sildenafil 50 mg on left ventricular filling pressures as evaluated 1 hr after sildenafil administration in patients with heart failure |
|
| placebo | Placebo Comparator | Inactive placebo prepared to mimic the appearance of sildenafil. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sildenafil | Drug | Changes in left ventricular filling pressure 1 hour after the administration of a single oral dose of sildenafil 50 mg. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Reduction of the Left Ventricular Filling Pressure in Association With Administration of Sildenafil | Left ventricular filling pressure was assessed by the ratio of the velocity of early mitral inflow (E) divided by the early tissue velocity (e). E/e | Left ventricular filling pressure was assessed 1 hr after oral administration of sildenafil |
| Measure | Description | Time Frame |
|---|---|---|
| The Distance Walked During the 6-minute Walk Test 1 hr After the Oral Administration of Sildenafil 50 mg. | A standardized course was used to determine the distance walked (meters) during a 6 min walk supervised by a nurse trained in performance of the test. | Measured 1 hr after oral administration of sildenafil 50 mg |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert C Bahler, MD | MetroHealth Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| MetroHealth Medical Center | Cleveland | Ohio | 44109 | United States |
More than 50 patients had to be excluded due to their already taking nitrates for their heart failure.
Patients were recruited from the Heart Failure Clinic at MetroHealth Medical Center over a 12 month interval. Recruitment was slow due to the fact that many of the patients were already perscirbed nitrates and so were ineligible for the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sildenafil Then Placebo | Effect of sildenafil on left ventricular filling pressures in patients with heart failure |
| FG001 | Placebo Then Sildenafil | Effect of Sildenafil on left ventricular function |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sildenafil First Placebo Second | Effect of sildenafil on left ventricular filling pressures in patients with heart failure |
| BG001 | Placebo First Sildenafil Second | Effect of placebo on left ventricular filling pressures in patients with heart failure |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Reduction of the Left Ventricular Filling Pressure in Association With Administration of Sildenafil | Left ventricular filling pressure was assessed by the ratio of the velocity of early mitral inflow (E) divided by the early tissue velocity (e). E/e | All patients (10) that completed the protocol were analyzed. | Posted | Mean | Standard Deviation | E/e' ratio | Left ventricular filling pressure was assessed 1 hr after oral administration of sildenafil |
|
The study took place over a 1 year interval
Patients were observered for any side effects or adverse reactions for 2 hrs following the administration of either sildenafil or placebo.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sildenafil First Then Placebo | Effect of sildenafil first on left ventricular filling pressures, then effect of placebo on left ventricular filling pressure |
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The study was limited by the small number of participants. Additionally, the inclusion criterion of a systolic pulmonary artery pressure of > 40 mmHg was no longer present in the majority of patients at the time they presented for study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Robert C. Bahler, MD | MetroHealth Medical Center | 216 778-2431 | rbahler@metrohealth.org |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D018487 | Ventricular Dysfunction, Left |
| D018754 | Ventricular Dysfunction |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000068677 | Sildenafil Citrate |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 |
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|
| Placebo | Other | Changes in left ventricular filling pressure 1 hour after oral administration of placebo |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | The Distance Walked During the 6-minute Walk Test 1 hr After the Oral Administration of Sildenafil 50 mg. | A standardized course was used to determine the distance walked (meters) during a 6 min walk supervised by a nurse trained in performance of the test. | Posted | Mean | Standard Deviation | meters | Measured 1 hr after oral administration of sildenafil 50 mg |
|
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| EG001 | Placebo First Then Sildenafil | Effect of placebo on left ventricular filing pressures, then effect of sildenafil on left ventricular filling pressure. | 0 | 5 | 0 | 5 |
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| Sulfur Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |