ADHFPhase 4Tra-HSS-FurNCT01419132
Troponin I Release After High Diuretic Doses
A Phase 4 study testing Furosemide in people with ADHF, run by University of Palermo at 3 sites in Italy.
Trial summary
High values of cardiac troponin (Ct) in acute heart failure (ADHF) identify patients (pts) at higher risk and worsened prognosis. A Ct increase during therapy indicates the need for more appropriate intervention, aimed at compensating cardiac disease and effectively minimizing myocardial wall stress and subsequent… Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- ADHF
- What is being tested?
- Furosemide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 3 sitesItaly
- Study dates
- Aug 2011to Sep 2011
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- signs/symptoms of heart failure;
- New York Heart Association (NYHA) functional Class III or IV on admission due to an exacerbation of symptoms with at least 1 class deterioration;
- evidence of systolic dysfunction on echocardiographic examination on admission (EF<45%);
- BNP levels on admission > 100pg/mL
Who cannot join
- NYHA class < III on admission or without a NYHA class improvement on discharge;
- acute coronary syndrome,
- pulmonary thromboembolism,
- cardiac tamponade,
- pericarditis,
- renal insufficiency (serum creatinine <2,5 mg/dL, BUN <60 mg/dL) or those on dialysis;
Show all 17Show fewer
- chronic liver disease,
- pleuro-pneumonia,
- blood and autoimmune diseases,
- concomitant other important co-morbidity,
- cerebral vascular disease,
- dementia,
- cancer,
- uncompensated diabetes,
- took non-steroid anti-inflammatory drugs (NSAID)
- declining to provide informed consent,
- patients requiring pacemaker implantation and those with issues of excessive alcohol consumption
Trial locations and contacts
3 sites in 1 country.
Italy3 sites
Department of Internal and Specialty Medicine
Palermo, Palermo, 90127
Gaspare PArrinello
Palermo, Palermo, 90127
GF Ingrasasia Hospital
Palermo, Palermo, 90132
About this study
Official title: Effects of High Furosemide Doses Alone or With Hypertonic Saline on Troponin I Myocardial Release in Acute Decompensated Heart Failure: a Double Blind Study.
High values of cardiac troponin (Ct) in acute heart failure (ADHF) identify patients (pts) at higher risk and worsened prognosis. A Ct increase during therapy indicates the need for more appropriate intervention, aimed at compensating cardiac disease and effectively minimizing myocardial wall stress and subsequent cytolysis. This study evaluated the effects of an intravenous high-dose of furosemide with or without small-volume hypertonic saline solution (HSS)on myocardial cytolysis in ADHF pts.
Read the detailed description
After randomization, all patients included in the study underwent a complete physical examination, including a careful check of HF signs and symptoms, including BW measurement (in the morning before breakfast), supine and standing blood pressure (BP [the mean of 3 measurements]), and heart rate (HR). Fasting blood samples were drawn to determine the serum levels of Na, K, Cl, bicarbonate, albumin, uric acid, creatinine, urea, and glycemia on a daily basis during hospitalization, and this was continued until a clinically compensated state was obtained. The total daily output of urine was collected for measuring levels of creatinine clearance, urinary Na and K. A chest radiograph, electrocardiogram, and echocardiogram (prior to commencing therapy and again when discharged. In addition, BNP and TNI plasma levels will be evaluated for all patients on entry and at discharge. Each patient provided written informed consent prior to participating in the study.
In order to determine GFR, the MDRD formula (Modification of Diet in Renal Disease), involving 4 parameters, was deployed. It provides an estimate of GFR comparable or superior to other formulae, with the advantage of not requiring any anthropometric measurements. According to the MDRD, GFR can be estimated using the following formula: GFR (ml/min/1.73m2) = 175 x {[serum creatinine (mg / dL or μmol/L/88.4)] -1.154 x {age (years) }-0.203 x 0.742 if female and 1.21 if Afro-American. The estimating of GFR by means of the MDRD formula is a useful and valid tool with which to obtain an index of kidney function.
The echocardiography M / B mode color Doppler will be performed with a Vivid 7 echocardiograph, with patients in a supine position and slightly left lateral decubitus. The mitral flow and the time taken for the wave to return to baseline (DTE) were evaluated from the apical 4 room positions, placing the sample volume of pulsed Doppler at the peak of the valve leaflets during the opening. Subsequently, the speed of early diastolic movement (Ea) of mitral annulus, obtained from the 4 room projection placing the sample volume of pulsed tissue Doppler onto lateral corner of the annulus, was assessed as an index of left ventricular relaxation. By measuring the Ea wave and the E / Ea ratio, the PCWP was evaluated in a quantitative way according to the following formulae:
PCWP = 1.24 E / Ea + 1.91 for those in sinus rhythm PCWP = 0.821 E / Ea + 6.489 for those in atrial fibrillation. Calculating dp/dt. The calculating of dp/dt was performed by a spectral analysis of mitral regurgitation at CW Doppler. Two points were chosen on the mitral regurgitation curve for the correct calculation of echocardiographic dp / dt: A: speed 1 m / sec = 4 mm Hg; and B: speed 3 m / sec = 36 mm Hg. The pressure gradient between these two point was reported to be 32 mmHg (A - B = 36 - 4 = 32). dP/dT was calculated by dividing the pressure gradient between the two points for the temporal distance between them: dP / dT = 32mmHg / T msec.
Bioelectrical impedance variables will be detected with an impedance plethysmograph using a previously-described methodology (18). This emitted an alternating sinusoidal electric current of 800 mA and an operating single frequency of 50 kHz; it which was calibrated each morning using a standard resistor supplied by the manufacturer. BIA is a method for detecting whole-body fluid overload and pulmonary congestion, based on the theory that the accumulation of whole-body or intrathoracic fluid will conduct an electrical current passing across the body or trunk more easily, leading to a decrease in whole-body or pulmonary bioimpedance. Bioimpedance is a combination of resistance (Rz) (ie, the opposition of an alternating current flowing through intra- and extra-cellular ionic solutions) and reactance (Xc) (ie, the capacitative component of tissue interfaces, cell membranes, and organelles). As previous described, in standard whole-body tetrapolar BIA, sensing electrodes were placed on: the dorsum of the wrist, a line between the radial and ulnar styloid processes, the dorsum of the ipsilateral foot, and on a line between the medial and lateral malleoli. Source electrodes were placed to overlie the head of the third metacarpal on the dorsum of the hand and the third metatarsal on the dorsum of the foot, on the same side as the sensing electrodes. The measurements will be performed on the right side of the body with the patients in a semi-orthopneic or supine position. According to the RzXc graph method of the BIA vector, the impedance measurement will be standardized according to the height (H) of the subject, expressing both Rz/H and Xc/H in ohm/meters, to establish the hydration state. Bioelectrical impedance measurements will be assessed twice by the same experienced operator and paired measurements for each patient were used in the analysis.
- Conditions
- ADHF
- Being tested
- Furosemide
- Keywords
- furosemide, hypertonic saline solution, troponin I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FurosemideDrug
Also called diuretics
125-250 mg furosemide bid
FurosemideDrug
Also called diuretics
125-250 mf furosemide bid
| Study group | Role | What they receive |
|---|---|---|
| High doses furosemide | Placebo comparator | administration of furosemide alone Receives: Drug: Furosemide |
| HSS plus furosemide | Experimental | administration of hypertonic saline solution plus high doses of furosemide bid Receives: Drug: Furosemide |
What is being measured
The primary outcome is the main question the study is designed to answer.
troponin I plasma levels (pg/ml)
troponin I will be evaluated at entry and at dicharge
Measured: participants will be followed for the duration of hospital stay, an expected average of 1 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2011 (estimated)
- Study startAug 2011
- Primary completionSep 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ADHFStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Palermo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gaspare Parrinello, University of Palermo
- Investigators
- Parrinello Gaspare, MD, Study chair, University of Palermo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01419132
- Sponsor's protocol ID
- Tra-HSS-Fur
- Other IDs
- 12/11 UNIPA-AOUP
- Acronym
- Tra-HSS-Fur
- Status last verified
- Oct 2011
- First submitted
- 15 Aug 2011
- Last updated
- 1 Nov 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Kociol RD, Pang PS, Gheorghiade M, Fonarow GC, O'Connor CM, Felker GM. Troponin elevation in heart failure prevalence, mechanisms, and clinical implications. J Am Coll Cardiol. 2010 Sep 28;56(14):1071-8. doi: 10.1016/j.jacc.2010.06.016.
PubMed 20863950Parrinello G, Paterna S, Di Pasquale P, Torres D, Mezzero M, Cardillo M, Fasullo S, La Rocca G, Licata G. Changes in estimating echocardiography pulmonary capillary wedge pressure after hypersaline plus furosemide versus furosemide alone in decompensated heart failure. J Card Fail. 2011 Apr;17(4):331-9. doi: 10.1016/j.cardfail.2010.11.003. Epub 2010 Dec 24.
PubMed 21440872Parrinello G, Di Pasquale P, Torres D, Cardillo M, Schimmenti C, Lupo U, Iatrino R, Petrantoni R, Montaina C, Giambanco S, Paterna S. Troponin I release after intravenous treatment with high furosemide doses plus hypertonic saline solution in decompensated heart failure trial (Tra-HSS-Fur). Am Heart J. 2012 Sep;164(3):351-7. doi: 10.1016/j.ahj.2012.05.025. Epub 2012 Aug 17.
PubMed 22980301
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of High Furosemide Doses Alone or With Hypertonic Saline on Troponin I Myocardial Release in Acute Decompensated Heart Failure: a Double Blind Study.
- ClinicalTrials.gov ID
- NCT01419132
- Acronym / sponsor ID
- Tra-HSS-Fur / Tra-HSS-Fur
- Conditions
- ADHF
- Keywords
- furosemide, hypertonic saline solution, troponin I
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of PalermoUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 17 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
High values of cardiac troponin (Ct) in acute heart failure (ADHF) identify patients (pts) at higher risk and worsened prognosis. A Ct increase during therapy indicates the need for more appropriate intervention, aimed at compensating cardiac disease and effectively minimizing myocardial wall stress and subsequent cytolysis. This study evaluated the effects of an intravenous high-dose of furosemide with or without small-volume hypertonic saline solution (HSS)on myocardial cytolysis in ADHF pts.
Detailed description
After randomization, all patients included in the study underwent a complete physical examination, including a careful check of HF signs and symptoms, including BW measurement (in the morning before breakfast), supine and standing blood pressure (BP [the mean of 3 measurements]), and heart rate (HR). Fasting blood samples were drawn to determine the serum levels of Na, K, Cl, bicarbonate, albumin, uric acid, creatinine, urea, and glycemia on a daily basis during hospitalization, and this was continued until a clinically compensated state was obtained. The total daily output of urine was collected for measuring levels of creatinine clearance, urinary Na and K. A chest radiograph, electrocardiogram, and echocardiogram (prior to commencing therapy and again when discharged. In addition, BNP and TNI plasma levels will be evaluated for all patients on entry and at discharge. Each patient provided written informed consent prior to participating in the study.
In order to determine GFR, the MDRD formula (Modification of Diet in Renal Disease), involving 4 parameters, was deployed. It provides an estimate of GFR comparable or superior to other formulae, with the advantage of not requiring any anthropometric measurements. According to the MDRD, GFR can be estimated using the following formula: GFR (ml/min/1.73m2) = 175 x {[serum creatinine (mg / dL or μmol/L/88.4)] -1.154 x {age (years) }-0.203 x 0.742 if female and 1.21 if Afro-American. The estimating of GFR by means of the MDRD formula is a useful and valid tool with which to obtain an index of kidney function.
The echocardiography M / B mode color Doppler will be performed with a Vivid 7 echocardiograph, with patients in a supine position and slightly left lateral decubitus. The mitral flow and the time taken for the wave to return to baseline (DTE) were evaluated from the apical 4 room positions, placing the sample volume of pulsed Doppler at the peak of the valve leaflets during the opening. Subsequently, the speed of early diastolic movement (Ea) of mitral annulus, obtained from the 4 room projection placing the sample volume of pulsed tissue Doppler onto lateral corner of the annulus, was assessed as an index of left ventricular relaxation. By measuring the Ea wave and the E / Ea ratio, the PCWP was evaluated in a quantitative way according to the following formulae:
PCWP = 1.24 E / Ea + 1.91 for those in sinus rhythm PCWP = 0.821 E / Ea + 6.489 for those in atrial fibrillation. Calculating dp/dt. The calculating of dp/dt was performed by a spectral analysis of mitral regurgitation at CW Doppler. Two points were chosen on the mitral regurgitation curve for the correct calculation of echocardiographic dp / dt: A: speed 1 m / sec = 4 mm Hg; and B: speed 3 m / sec = 36 mm Hg. The pressure gradient between these two point was reported to be 32 mmHg (A - B = 36 - 4 = 32). dP/dT was calculated by dividing the pressure gradient between the two points for the temporal distance between them: dP / dT = 32mmHg / T msec.
Bioelectrical impedance variables will be detected with an impedance plethysmograph using a previously-described methodology (18). This emitted an alternating sinusoidal electric current of 800 mA and an operating single frequency of 50 kHz; it which was calibrated each morning using a standard resistor supplied by the manufacturer. BIA is a method for detecting whole-body fluid overload and pulmonary congestion, based on the theory that the accumulation of whole-body or intrathoracic fluid will conduct an electrical current passing across the body or trunk more easily, leading to a decrease in whole-body or pulmonary bioimpedance. Bioimpedance is a combination of resistance (Rz) (ie, the opposition of an alternating current flowing through intra- and extra-cellular ionic solutions) and reactance (Xc) (ie, the capacitative component of tissue interfaces, cell membranes, and organelles). As previous described, in standard whole-body tetrapolar BIA, sensing electrodes were placed on: the dorsum of the wrist, a line between the radial and ulnar styloid processes, the dorsum of the ipsilateral foot, and on a line between the medial and lateral malleoli. Source electrodes were placed to overlie the head of the third metacarpal on the dorsum of the hand and the third metatarsal on the dorsum of the foot, on the same side as the sensing electrodes. The measurements will be performed on the right side of the body with the patients in a semi-orthopneic or supine position. According to the RzXc graph method of the BIA vector, the impedance measurement will be standardized according to the height (H) of the subject, expressing both Rz/H and Xc/H in ohm/meters, to establish the hydration state. Bioelectrical impedance measurements will be assessed twice by the same experienced operator and paired measurements for each patient were used in the analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High doses furosemide | Placebo comparator | Drug: Furosemideadministration of furosemide alone |
| HSS plus furosemide | Experimental | Drug: Furosemideadministration of hypertonic saline solution plus high doses of furosemide bid |
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- signs/symptoms of heart failure;
- New York Heart Association (NYHA) functional Class III or IV on admission due to an exacerbation of symptoms with at least 1 class deterioration;
- evidence of systolic dysfunction on echocardiographic examination on admission (EF<45%);
- BNP levels on admission > 100pg/mL
Key exclusion criteria (17 listed)
- NYHA class < III on admission or without a NYHA class improvement on discharge;
- acute coronary syndrome,
- pulmonary thromboembolism,
- cardiac tamponade,
- pericarditis,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FurosemideAlso: diuretics125-250 mg furosemide bid | Drug | HSS plus furosemide |
| FurosemideAlso: diuretics125-250 mf furosemide bid | Drug | High doses furosemide |
Primary outcome
troponin I plasma levels (pg/ml)
Time frame: participants will be followed for the duration of hospital stay, an expected average of 1 weeks
troponin I will be evaluated at entry and at dicharge
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2011.
- Results publication: PubMed 20863950Kociol RD, Pang PS, Gheorghiade M, Fonarow GC, O'Connor CM, Felker GM. Troponin elevation in heart failure prevalence, mechanisms, and clinical implications. J Am Coll Cardiol. 2010 Sep 28;56(14):1071-8. doi: 10.1016/j.jacc.2010.06.016.
- Results publication: PubMed 21440872Parrinello G, Paterna S, Di Pasquale P, Torres D, Mezzero M, Cardillo M, Fasullo S, La Rocca G, Licata G. Changes in estimating echocardiography pulmonary capillary wedge pressure after hypersaline plus furosemide versus furosemide alone in decompensated heart failure. J Card Fail. 2011 Apr;17(4):331-9. doi: 10.1016/j.cardfail.2010.11.003. Epub 2010 Dec 24.
- Derived from this study: PubMed 22980301Parrinello G, Di Pasquale P, Torres D, Cardillo M, Schimmenti C, Lupo U, Iatrino R, Petrantoni R, Montaina C, Giambanco S, Paterna S. Troponin I release after intravenous treatment with high furosemide doses plus hypertonic saline solution in decompensated heart failure trial (Tra-HSS-Fur). Am Heart J. 2012 Sep;164(3):351-7. doi: 10.1016/j.ahj.2012.05.025. Epub 2012 Aug 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Parrinello Gaspare, MD study chair
University of Palermo
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Furosemide in people with ADHF, run by University of Palermo at 3 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
troponin I plasma levels (pg/ml) (time frame: participants will be followed for the duration of hospital stay, an expected average of 1 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01419132, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2011.