Trial Outcomes & Findings for Sildenafil To Prevent Clot (NCT NCT03199612)
NCT ID: NCT03199612
Last Updated: 2024-07-10
Results Overview
During the study period platelet activation and aggregation will be measured from drawn blood samples. Platelet rich plasma will be isolated from these samples and platelet aggregometry will be used to measure platelet activation and aggregation. Platelet activation and aggregation is measured as an area under the curve (AUC) derived as the resistance (ohms) x time (s). There is no reference range for ADP induced AUC. Higher values of AUC indicate greater platelet aggregation.
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
20 participants
Primary outcome timeframe
Baseline, day 8 and day 15
Results posted on
2024-07-10
Participant Flow
Participant milestones
| Measure |
Sildenafil
Baseline blood samples and study measurements will be acquired. Then 20 mg of the study drug will be administered. Then BP will be recorded every 30 minutes for two hours. If BP is stable (drop is \< 5 mmHg after 2 hours and patient is asymptomatic), patient will proceed to take 20 mg of the study drug every 8 hours. The patient will return to clinic on day 8 and 20 mg of the study drug will be administered. After 2 hours blood samples and study measurements will be collected and the patient will resume 20 mg of the study for the next two doses. The patient will return for a third clinic visit on the next day and if BP is in the acceptable range, 40 mg of the study drug will be administered. If BP remains stable for 2 hours, then the patient will continue taking 40 mg every 8 hours. The patient will return to clinic on day 15 for a final study visit and will be given the last 40 mg dose of the study drug and after 2 hours blood samples and study measurements will be taken.
Sildenafil: To conduct a randomized placebo controlled study to test the hypothesis that platelet activation and aggregation during ongoing low level hemolysis in outpatients on chronic continuous flow (CF) pump support can be reduced by sildenafil.
|
Placebo Oral Tablet
Negative control to understand the potential changes in platelet activation and aggregation in comparison to sildenafil.
Placebo Oral Tablet: Negative control to understand the potential changes in platelet activation adn aggregation in comparison to sildenafil.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
|
Overall Study
COMPLETED
|
9
|
10
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Sildenafil
Baseline blood samples and study measurements will be acquired. Then 20 mg of the study drug will be administered. Then BP will be recorded every 30 minutes for two hours. If BP is stable (drop is \< 5 mmHg after 2 hours and patient is asymptomatic), patient will proceed to take 20 mg of the study drug every 8 hours. The patient will return to clinic on day 8 and 20 mg of the study drug will be administered. After 2 hours blood samples and study measurements will be collected and the patient will resume 20 mg of the study for the next two doses. The patient will return for a third clinic visit on the next day and if BP is in the acceptable range, 40 mg of the study drug will be administered. If BP remains stable for 2 hours, then the patient will continue taking 40 mg every 8 hours. The patient will return to clinic on day 15 for a final study visit and will be given the last 40 mg dose of the study drug and after 2 hours blood samples and study measurements will be taken.
Sildenafil: To conduct a randomized placebo controlled study to test the hypothesis that platelet activation and aggregation during ongoing low level hemolysis in outpatients on chronic continuous flow (CF) pump support can be reduced by sildenafil.
|
Placebo Oral Tablet
Negative control to understand the potential changes in platelet activation and aggregation in comparison to sildenafil.
Placebo Oral Tablet: Negative control to understand the potential changes in platelet activation adn aggregation in comparison to sildenafil.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
Baseline Characteristics
Sildenafil To Prevent Clot
Baseline characteristics by cohort
| Measure |
Sildenafil
n=10 Participants
Baseline blood samples and study measurements will be acquired. Then 20 mg of the study drug will be administered. Then BP will be recorded every 30 minutes for two hours. If BP is stable (drop is \< 5 mmHg after 2 hours and patient is asymptomatic), patient will proceed to take 20 mg of the study drug every 8 hours. The patient will return to clinic on day 8 and 20 mg of the study drug will be administered. After 2 hours blood samples and study measurements will be collected and the patient will resume 20 mg of the study for the next two doses. The patient will return for a third clinic visit on the next day and if BP is in the acceptable range, 40 mg of the study drug will be administered. If BP remains stable for 2 hours, then the patient will continue taking 40 mg every 8 hours. The patient will return to clinic on day 15 for a final study visit and will be given the last 40 mg dose of the study drug and after 2 hours blood samples and study measurements will be taken.
Sildenafil: To conduct a randomized placebo controlled study to test the hypothesis that platelet activation and aggregation during ongoing low level hemolysis in outpatients on chronic CF pump support can be reduced by sildenafil.
|
Placebo Oral Tablet
n=10 Participants
Negative control to understand the potential changes in platelet activation and aggregation in comparison to sildenafil.
Placebo Oral Tablet: Negative control to understand the potential changes in platelet activation and aggregation in comparison to sildenafil.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55 years
n=5 Participants
|
56 years
n=7 Participants
|
55 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Non Hispanic Black
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Non Hispanic White
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
10 participants
n=7 Participants
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, day 8 and day 15Population: 1 participant in the sildenafil group was not able to tolerate 40 mg and did not reach the 15 day endpoint.
During the study period platelet activation and aggregation will be measured from drawn blood samples. Platelet rich plasma will be isolated from these samples and platelet aggregometry will be used to measure platelet activation and aggregation. Platelet activation and aggregation is measured as an area under the curve (AUC) derived as the resistance (ohms) x time (s). There is no reference range for ADP induced AUC. Higher values of AUC indicate greater platelet aggregation.
Outcome measures
| Measure |
Sildenafil
n=10 Participants
Baseline blood samples and study measurements will be acquired. Then 20 mg of the study drug will be administered. Then BP will be recorded every 30 minutes for two hours. If BP is stable (drop is \< 5 mmHg after 2 hours and patient is asymptomatic), patient will proceed to take 20 mg of the study drug every 8 hours. The patient will return to clinic on day 8 and 20 mg of the study drug will be administered. After 2 hours blood samples and study measurements will be collected and the patient will resume 20 mg of the study for the next two doses. The patient will return for a third clinic visit on the next day and if BP is in the acceptable range, 40 mg of the study drug will be administered. If BP remains stable for 2 hours, then the patient will continue taking 40 mg every 8 hours. The patient will return to clinic on day 15 for a final study visit and will be given the last 40 mg dose of the study drug and after 2 hours blood samples and study measurements will be taken.
Sildenafil: To conduct a randomized placebo controlled study to test the hypothesis that platelet activation and aggregation during ongoing low level hemolysis in outpatients on chronic CF pump support can be reduced by sildenafil.
|
Placebo Oral Tablet
n=10 Participants
Negative control to understand the potential changes in platelet activation and aggregation in comparison to sildenafil.
Placebo Oral Tablet: Negative control to understand the potential changes in platelet activation adn aggregation in comparison to sildenafil.
|
|---|---|---|
|
Area Under the Curve for Adenosine Diphosphate (ADP)
Baseline
|
50 omhs x seconds (AUC)
Interval 35.0 to 67.0
|
20 omhs x seconds (AUC)
Interval 4.0 to 35.0
|
|
Area Under the Curve for Adenosine Diphosphate (ADP)
Day 8
|
50 omhs x seconds (AUC)
Interval 25.0 to 60.0
|
6 omhs x seconds (AUC)
Interval 0.3 to 40.0
|
|
Area Under the Curve for Adenosine Diphosphate (ADP)
Day 15
|
38 omhs x seconds (AUC)
Interval 19.0 to 69.0
|
27 omhs x seconds (AUC)
Interval 2.0 to 60.0
|
SECONDARY outcome
Timeframe: Baseline, day 8 and day 15Population: 1 participant in the sildenafil group was not able to tolerate 40 mg and did not reach the 15 day endpoint.
During the study period pro-thrombotic inflammatory markers, including hs CRP (mg/L) in serum will be measured by ELISA. The upper limit of normal reference for hs CRP is 0.5 mg/dL. Higher values of hs CRP indicate greater pro-thrombotic inflammation.
Outcome measures
| Measure |
Sildenafil
n=10 Participants
Baseline blood samples and study measurements will be acquired. Then 20 mg of the study drug will be administered. Then BP will be recorded every 30 minutes for two hours. If BP is stable (drop is \< 5 mmHg after 2 hours and patient is asymptomatic), patient will proceed to take 20 mg of the study drug every 8 hours. The patient will return to clinic on day 8 and 20 mg of the study drug will be administered. After 2 hours blood samples and study measurements will be collected and the patient will resume 20 mg of the study for the next two doses. The patient will return for a third clinic visit on the next day and if BP is in the acceptable range, 40 mg of the study drug will be administered. If BP remains stable for 2 hours, then the patient will continue taking 40 mg every 8 hours. The patient will return to clinic on day 15 for a final study visit and will be given the last 40 mg dose of the study drug and after 2 hours blood samples and study measurements will be taken.
Sildenafil: To conduct a randomized placebo controlled study to test the hypothesis that platelet activation and aggregation during ongoing low level hemolysis in outpatients on chronic CF pump support can be reduced by sildenafil.
|
Placebo Oral Tablet
n=10 Participants
Negative control to understand the potential changes in platelet activation and aggregation in comparison to sildenafil.
Placebo Oral Tablet: Negative control to understand the potential changes in platelet activation adn aggregation in comparison to sildenafil.
|
|---|---|---|
|
Pro-thrombotic Inflammation as Measured by High-sensitivity C-reactive Protein (hs CRP)
Baseline
|
2.2 mg/L
Interval 1.31 to 3.63
|
2.2 mg/L
Interval 1.0 to 3.1
|
|
Pro-thrombotic Inflammation as Measured by High-sensitivity C-reactive Protein (hs CRP)
Day 8
|
2.9 mg/L
Interval 1.75 to 4.05
|
2.20 mg/L
Interval 1.04 to 3.07
|
|
Pro-thrombotic Inflammation as Measured by High-sensitivity C-reactive Protein (hs CRP)
Day 15
|
2.57 mg/L
Interval 0.88 to 5.02
|
2.2 mg/L
Interval 0.75 to 3.98
|
SECONDARY outcome
Timeframe: Baseline, day 8 and day 15Population: 1 participant in the sildenafil group was not able to tolerate 40 mg and did not reach the 15 day endpoint.
During the study period pro-thrombotic inflammatory markers including fibrinogen (mg/dL) will be measured by ELISA. The upper limit of normal reference for fibrinogen is 187-502 mg/dl. Higher values of fibrinogen indicate greater thrombo-inflammation.
Outcome measures
| Measure |
Sildenafil
n=10 Participants
Baseline blood samples and study measurements will be acquired. Then 20 mg of the study drug will be administered. Then BP will be recorded every 30 minutes for two hours. If BP is stable (drop is \< 5 mmHg after 2 hours and patient is asymptomatic), patient will proceed to take 20 mg of the study drug every 8 hours. The patient will return to clinic on day 8 and 20 mg of the study drug will be administered. After 2 hours blood samples and study measurements will be collected and the patient will resume 20 mg of the study for the next two doses. The patient will return for a third clinic visit on the next day and if BP is in the acceptable range, 40 mg of the study drug will be administered. If BP remains stable for 2 hours, then the patient will continue taking 40 mg every 8 hours. The patient will return to clinic on day 15 for a final study visit and will be given the last 40 mg dose of the study drug and after 2 hours blood samples and study measurements will be taken.
Sildenafil: To conduct a randomized placebo controlled study to test the hypothesis that platelet activation and aggregation during ongoing low level hemolysis in outpatients on chronic CF pump support can be reduced by sildenafil.
|
Placebo Oral Tablet
n=10 Participants
Negative control to understand the potential changes in platelet activation and aggregation in comparison to sildenafil.
Placebo Oral Tablet: Negative control to understand the potential changes in platelet activation adn aggregation in comparison to sildenafil.
|
|---|---|---|
|
Pro-thrombotic Inflammation as Measured by Fibrinogen
Baseline
|
355 mg/dl
Interval 313.0 to 388.0
|
334 mg/dl
Interval 277.0 to 372.0
|
|
Pro-thrombotic Inflammation as Measured by Fibrinogen
Day 8
|
392 mg/dl
Interval 324.0 to 434.0
|
311 mg/dl
Interval 295.0 to 345.0
|
|
Pro-thrombotic Inflammation as Measured by Fibrinogen
Day 15
|
398 mg/dl
Interval 324.0 to 440.0
|
345 mg/dl
Interval 292.0 to 389.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, day 8 and day 15Population: 1 participant in the sildenafil group was not able to tolerate 40 mg and did not reach the 15 day endpoint.
Mediator of vascular remodeling. This is a relative unit and there is no reference range in the context of magnetically levitated left ventricular assist device support. A higher Angiopoietin-2 to Angiopoietin-1 ratio indicates greater microvascular remodeling and inflammation.
Outcome measures
| Measure |
Sildenafil
n=10 Participants
Baseline blood samples and study measurements will be acquired. Then 20 mg of the study drug will be administered. Then BP will be recorded every 30 minutes for two hours. If BP is stable (drop is \< 5 mmHg after 2 hours and patient is asymptomatic), patient will proceed to take 20 mg of the study drug every 8 hours. The patient will return to clinic on day 8 and 20 mg of the study drug will be administered. After 2 hours blood samples and study measurements will be collected and the patient will resume 20 mg of the study for the next two doses. The patient will return for a third clinic visit on the next day and if BP is in the acceptable range, 40 mg of the study drug will be administered. If BP remains stable for 2 hours, then the patient will continue taking 40 mg every 8 hours. The patient will return to clinic on day 15 for a final study visit and will be given the last 40 mg dose of the study drug and after 2 hours blood samples and study measurements will be taken.
Sildenafil: To conduct a randomized placebo controlled study to test the hypothesis that platelet activation and aggregation during ongoing low level hemolysis in outpatients on chronic CF pump support can be reduced by sildenafil.
|
Placebo Oral Tablet
n=10 Participants
Negative control to understand the potential changes in platelet activation and aggregation in comparison to sildenafil.
Placebo Oral Tablet: Negative control to understand the potential changes in platelet activation adn aggregation in comparison to sildenafil.
|
|---|---|---|
|
Serum Angiopoietin-2 to Angiopoietin-1 Ratio
Baseline
|
0.10 ratio
Interval 0.08 to 0.13
|
0.11 ratio
Interval 0.09 to 0.12
|
|
Serum Angiopoietin-2 to Angiopoietin-1 Ratio
Day 8
|
0.09 ratio
Interval 0.06 to 0.15
|
0.12 ratio
Interval 0.09 to 0.13
|
|
Serum Angiopoietin-2 to Angiopoietin-1 Ratio
Day 15
|
0.06 ratio
Interval 0.06 to 0.09
|
0.11 ratio
Interval 0.08 to 0.15
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, day 8 and day 15Population: 1 participant in the sildenafil group was not able to tolerate 40 mg and did not reach the 15 day endpoint.
Mediator of vascular fibrosis. The normal reference is 1-2 pg/ml. Higher values indicate greater deviation from normal.
Outcome measures
| Measure |
Sildenafil
n=10 Participants
Baseline blood samples and study measurements will be acquired. Then 20 mg of the study drug will be administered. Then BP will be recorded every 30 minutes for two hours. If BP is stable (drop is \< 5 mmHg after 2 hours and patient is asymptomatic), patient will proceed to take 20 mg of the study drug every 8 hours. The patient will return to clinic on day 8 and 20 mg of the study drug will be administered. After 2 hours blood samples and study measurements will be collected and the patient will resume 20 mg of the study for the next two doses. The patient will return for a third clinic visit on the next day and if BP is in the acceptable range, 40 mg of the study drug will be administered. If BP remains stable for 2 hours, then the patient will continue taking 40 mg every 8 hours. The patient will return to clinic on day 15 for a final study visit and will be given the last 40 mg dose of the study drug and after 2 hours blood samples and study measurements will be taken.
Sildenafil: To conduct a randomized placebo controlled study to test the hypothesis that platelet activation and aggregation during ongoing low level hemolysis in outpatients on chronic CF pump support can be reduced by sildenafil.
|
Placebo Oral Tablet
n=10 Participants
Negative control to understand the potential changes in platelet activation and aggregation in comparison to sildenafil.
Placebo Oral Tablet: Negative control to understand the potential changes in platelet activation adn aggregation in comparison to sildenafil.
|
|---|---|---|
|
Concentration of Serum Endothelin-1
Baseline
|
2.56 pg/ml
Interval 2.35 to 2.78
|
2.78 pg/ml
Interval 2.18 to 3.73
|
|
Concentration of Serum Endothelin-1
Day 8
|
2.27 pg/ml
Interval 1.93 to 2.64
|
2.59 pg/ml
Interval 2.1 to 3.93
|
|
Concentration of Serum Endothelin-1
Day 15
|
1.64 pg/ml
Interval 1.62 to 2.09
|
2.66 pg/ml
Interval 2.03 to 3.2
|
Adverse Events
Sildenafil
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo Oral Tablet
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Sildenafil
n=10 participants at risk
Baseline blood samples and study measurements will be acquired. Then 20 mg of the study drug will be administered. Then BP will be recorded every 30 minutes for two hours. If BP is stable (drop is \< 5 mmHg after 2 hours and patient is asymptomatic), patient will proceed to take 20 mg of the study drug every 8 hours. The patient will return to clinic on day 8 and 20 mg of the study drug will be administered. After 2 hours blood samples and study measurements will be collected and the patient will resume 20 mg of the study for the next two doses. The patient will return for a third clinic visit on the next day and if BP is in the acceptable range, 40 mg of the study drug will be administered. If BP remains stable for 2 hours, then the patient will continue taking 40 mg every 8 hours. The patient will return to clinic on day 15 for a final study visit and will be given the last 40 mg dose of the study drug and after 2 hours blood samples and study measurements will be taken.
Sildenafil: To conduct a randomized placebo controlled study to test the hypothesis that platelet activation and aggregation during ongoing low level hemolysis in outpatients on chronic CF pump support can be reduced by sildenafil.
|
Placebo Oral Tablet
n=10 participants at risk
Negative control to understand the potential changes in platelet activation and aggregation in comparison to sildenafil.
Placebo Oral Tablet: Negative control to understand the potential changes in platelet activation adn aggregation in comparison to sildenafil.
|
|---|---|---|
|
Nervous system disorders
Headache
|
10.0%
1/10 • Number of events 1 • 15 days
|
0.00%
0/10 • 15 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place