Trial Outcomes & Findings for Nitroglycerin vs. Furosemide Using Lung Ultrasound Pilot Trial (NCT NCT03259165)
NCT ID: NCT03259165
Last Updated: 2024-08-20
Results Overview
The total number of B-lines at the conclusion of ED AHF management or maximum of 6 hours after enrollment, whichever comes first.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
52 participants
Primary outcome timeframe
During the ED phase of management, no more than 6 hours
Results posted on
2024-08-20
Participant Flow
Participant milestones
| Measure |
Nitrate Intense Strategy
Patients randomized to the Nitrate intense strategy will be treated according to protocol with nitrates in combination with IV loop diuretics. This protocol only involves therapies used in everyday AHF clinical practice.
Nitrates: For patients randomized to the Nitrate intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. IV furosemide (unless already given) (All patients receive at minimum 20 mg IV furosemide or equivalent)
2. SL nitroglycerin (400 ucg) will be given every 5 minutes, a total of three times. (May be repeated) (Held if SBP decreases to \< 120 mmHg)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
Diuretic Intense Strategy
Patients randomized to the Diuretic intense strategy will be treated according to protocol with IV loop diuretics in combination with nitrates. This protocol only involves therapies used in everyday AHF clinical practice.
Loop Diuretics: For patients randomized to the Diuretic intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. Patients receive 1 inch topical nitropaste
2. IV Loop diuretic dose = patients total oral dose (max dose of 200 mg IV)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
|---|---|---|
|
Overall Study
STARTED
|
27
|
25
|
|
Overall Study
COMPLETED
|
26
|
24
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Nitrate Intense Strategy
Patients randomized to the Nitrate intense strategy will be treated according to protocol with nitrates in combination with IV loop diuretics. This protocol only involves therapies used in everyday AHF clinical practice.
Nitrates: For patients randomized to the Nitrate intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. IV furosemide (unless already given) (All patients receive at minimum 20 mg IV furosemide or equivalent)
2. SL nitroglycerin (400 ucg) will be given every 5 minutes, a total of three times. (May be repeated) (Held if SBP decreases to \< 120 mmHg)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
Diuretic Intense Strategy
Patients randomized to the Diuretic intense strategy will be treated according to protocol with IV loop diuretics in combination with nitrates. This protocol only involves therapies used in everyday AHF clinical practice.
Loop Diuretics: For patients randomized to the Diuretic intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. Patients receive 1 inch topical nitropaste
2. IV Loop diuretic dose = patients total oral dose (max dose of 200 mg IV)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
|---|---|---|
|
Overall Study
COVID 19 pandemic
|
1
|
1
|
Baseline Characteristics
Nitroglycerin vs. Furosemide Using Lung Ultrasound Pilot Trial
Baseline characteristics by cohort
| Measure |
Nitrate Intense Strategy
n=27 Participants
Patients randomized to the Nitrate intense strategy will be treated according to protocol with nitrates in combination with IV loop diuretics. This protocol only involves therapies used in everyday AHF clinical practice.
Nitrates: For patients randomized to the Nitrate intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. IV furosemide (unless already given) (All patients receive at minimum 20 mg IV furosemide or equivalent)
2. SL nitroglycerin (400 ucg) will be given every 5 minutes, a total of three times. (May be repeated) (Held if SBP decreases to \< 120 mmHg)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
Diuretic Intense Strategy
n=25 Participants
Patients randomized to the Diuretic intense strategy will be treated according to protocol with IV loop diuretics in combination with nitrates. This protocol only involves therapies used in everyday AHF clinical practice.
Loop Diuretics: For patients randomized to the Diuretic intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. Patients receive 1 inch topical nitropaste
2. IV Loop diuretic dose = patients total oral dose (max dose of 200 mg IV)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
Total
n=52 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
19 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
26 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
27 participants
n=5 Participants
|
25 participants
n=7 Participants
|
52 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: During the ED phase of management, no more than 6 hoursPopulation: The trial was halted prematurely because of the COVID-19 pandemic. There is insufficient funding for data to be analyzed properly, at the time of this submission. Of the original 52 patients, only 9 in the Nitrate Arm and 7 in the Diuretic Intense arm had reported data of a LUS performed at the completion of ED treatment (t6)
The total number of B-lines at the conclusion of ED AHF management or maximum of 6 hours after enrollment, whichever comes first.
Outcome measures
| Measure |
Nitrate Intense Strategy
n=9 Participants
Patients randomized to the Nitrate intense strategy will be treated according to protocol with nitrates in combination with IV loop diuretics. This protocol only involves therapies used in everyday AHF clinical practice.
Nitrates: For patients randomized to the Nitrate intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. IV furosemide (unless already given) (All patients receive at minimum 20 mg IV furosemide or equivalent)
2. SL nitroglycerin (400 ucg) will be given every 5 minutes, a total of three times. (May be repeated) (Held if SBP decreases to \< 120 mmHg)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
Diuretic Intense Strategy
n=7 Participants
Patients randomized to the Diuretic intense strategy will be treated according to protocol with IV loop diuretics in combination with nitrates. This protocol only involves therapies used in everyday AHF clinical practice.
Loop Diuretics: For patients randomized to the Diuretic intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. Patients receive 1 inch topical nitropaste
2. IV Loop diuretic dose = patients total oral dose (max dose of 200 mg IV)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
|---|---|---|
|
The Total Number of B-lines at the Conclusion of ED AHF Management
|
29 Number of B-lines
Standard Deviation 22.5
|
32 Number of B-lines
Standard Deviation 19.4
|
SECONDARY outcome
Timeframe: During the ED phase of management, no more than 6 hoursPopulation: • The trial was halted prematurely due to the COVID-19 pandemic. There is insufficient funding for data to be analyzed properly at the time of this submission. Only 15 patients had data available to report
A patient reported measurement of dyspnea using 7-point Likert scales in a standardized position, ranging from Markedly worse, Moderately Worse, Minimally Worse, No Change to Minimally Improved, Moderately Improved, Markedly Improved
Outcome measures
| Measure |
Nitrate Intense Strategy
n=10 Participants
Patients randomized to the Nitrate intense strategy will be treated according to protocol with nitrates in combination with IV loop diuretics. This protocol only involves therapies used in everyday AHF clinical practice.
Nitrates: For patients randomized to the Nitrate intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. IV furosemide (unless already given) (All patients receive at minimum 20 mg IV furosemide or equivalent)
2. SL nitroglycerin (400 ucg) will be given every 5 minutes, a total of three times. (May be repeated) (Held if SBP decreases to \< 120 mmHg)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
Diuretic Intense Strategy
n=5 Participants
Patients randomized to the Diuretic intense strategy will be treated according to protocol with IV loop diuretics in combination with nitrates. This protocol only involves therapies used in everyday AHF clinical practice.
Loop Diuretics: For patients randomized to the Diuretic intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. Patients receive 1 inch topical nitropaste
2. IV Loop diuretic dose = patients total oral dose (max dose of 200 mg IV)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
|---|---|---|
|
Dyspnea Assessment
Markedly Improved
|
3 participants
|
1 participants
|
|
Dyspnea Assessment
Moderately Improved
|
1 participants
|
3 participants
|
|
Dyspnea Assessment
Minimally Improved
|
4 participants
|
0 participants
|
|
Dyspnea Assessment
No Change
|
1 participants
|
1 participants
|
|
Dyspnea Assessment
Minimally Worse
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: During the ED phase of management, no more than 6 hoursPopulation: • The trial was halted prematurely due to the COVID-19 pandemic. There is insufficient funding for data to be analyzed properly at the time of this submission. Only 16 patients had reported data for this endpoint
B-lines \<= 15 at the conclusion of ED AHF management or maximum of 6 hours after enrollment, whichever comes first
Outcome measures
| Measure |
Nitrate Intense Strategy
n=9 Participants
Patients randomized to the Nitrate intense strategy will be treated according to protocol with nitrates in combination with IV loop diuretics. This protocol only involves therapies used in everyday AHF clinical practice.
Nitrates: For patients randomized to the Nitrate intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. IV furosemide (unless already given) (All patients receive at minimum 20 mg IV furosemide or equivalent)
2. SL nitroglycerin (400 ucg) will be given every 5 minutes, a total of three times. (May be repeated) (Held if SBP decreases to \< 120 mmHg)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
Diuretic Intense Strategy
n=7 Participants
Patients randomized to the Diuretic intense strategy will be treated according to protocol with IV loop diuretics in combination with nitrates. This protocol only involves therapies used in everyday AHF clinical practice.
Loop Diuretics: For patients randomized to the Diuretic intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. Patients receive 1 inch topical nitropaste
2. IV Loop diuretic dose = patients total oral dose (max dose of 200 mg IV)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
|---|---|---|
|
B-lines <= 15 at the Conclusion of ED AHF Management
|
2 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up through 30 days post dischargeTotal days alive and out of hospital through 30 days post-discharge
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up through 30 days post dischargeOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Throughout hospitalization, on average 5-7 daysOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up through 30 days post dischargeOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 30 days post dischargeOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: From admission to pre-discharge from the hospital, on average 5 to 7 daysPhysical exam includes peripheral edema, jugular venous distention, pulmonary and cardiac auscultation
Outcome measures
Outcome data not reported
Adverse Events
Nitrate Intense Strategy
Serious events: 0 serious events
Other events: 3 other events
Deaths: 1 deaths
Diuretic Intense Strategy
Serious events: 1 serious events
Other events: 1 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Nitrate Intense Strategy
n=27 participants at risk
Patients randomized to the Nitrate intense strategy will be treated according to protocol with nitrates in combination with IV loop diuretics. This protocol only involves therapies used in everyday AHF clinical practice.
Nitrates: For patients randomized to the Nitrate intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. IV furosemide (unless already given) (All patients receive at minimum 20 mg IV furosemide or equivalent)
2. SL nitroglycerin (400 ucg) will be given every 5 minutes, a total of three times. (May be repeated) (Held if SBP decreases to \< 120 mmHg)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
Diuretic Intense Strategy
n=25 participants at risk
Patients randomized to the Diuretic intense strategy will be treated according to protocol with IV loop diuretics in combination with nitrates. This protocol only involves therapies used in everyday AHF clinical practice.
Loop Diuretics: For patients randomized to the Diuretic intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. Patients receive 1 inch topical nitropaste
2. IV Loop diuretic dose = patients total oral dose (max dose of 200 mg IV)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
|---|---|---|
|
Cardiac disorders
Death
|
0.00%
0/27 • The study period during which AEs must be reported begins after informed consent is obtained and initiation of study treatment and for 5 days after ending study treatment. Patients will be followed for 30 days for ED visits, re-hospitalization, and mortality. Subject's hospital discharge summaries will be examined at hospital discharge and all non-exempt AEs will be investigated by examining necessary medical records.
|
4.0%
1/25 • Number of events 1 • The study period during which AEs must be reported begins after informed consent is obtained and initiation of study treatment and for 5 days after ending study treatment. Patients will be followed for 30 days for ED visits, re-hospitalization, and mortality. Subject's hospital discharge summaries will be examined at hospital discharge and all non-exempt AEs will be investigated by examining necessary medical records.
|
Other adverse events
| Measure |
Nitrate Intense Strategy
n=27 participants at risk
Patients randomized to the Nitrate intense strategy will be treated according to protocol with nitrates in combination with IV loop diuretics. This protocol only involves therapies used in everyday AHF clinical practice.
Nitrates: For patients randomized to the Nitrate intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. IV furosemide (unless already given) (All patients receive at minimum 20 mg IV furosemide or equivalent)
2. SL nitroglycerin (400 ucg) will be given every 5 minutes, a total of three times. (May be repeated) (Held if SBP decreases to \< 120 mmHg)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
Diuretic Intense Strategy
n=25 participants at risk
Patients randomized to the Diuretic intense strategy will be treated according to protocol with IV loop diuretics in combination with nitrates. This protocol only involves therapies used in everyday AHF clinical practice.
Loop Diuretics: For patients randomized to the Diuretic intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
1. Patients receive 1 inch topical nitropaste
2. IV Loop diuretic dose = patients total oral dose (max dose of 200 mg IV)
3. Reassessment every 2 hours. If LUS B-lines \>15, repeat step 2. If \< 15, stop algorithm.
|
|---|---|---|
|
Renal and urinary disorders
CTCAE
|
11.1%
3/27 • Number of events 3 • The study period during which AEs must be reported begins after informed consent is obtained and initiation of study treatment and for 5 days after ending study treatment. Patients will be followed for 30 days for ED visits, re-hospitalization, and mortality. Subject's hospital discharge summaries will be examined at hospital discharge and all non-exempt AEs will be investigated by examining necessary medical records.
|
4.0%
1/25 • Number of events 1 • The study period during which AEs must be reported begins after informed consent is obtained and initiation of study treatment and for 5 days after ending study treatment. Patients will be followed for 30 days for ED visits, re-hospitalization, and mortality. Subject's hospital discharge summaries will be examined at hospital discharge and all non-exempt AEs will be investigated by examining necessary medical records.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place