Acute Heart FailurePhase 4diurHFNCT01441245
Loop Diuretics Administration and Acute Heart Failure
A Phase 4 study testing furosemide infusion in people with Acute Heart Failure, run by University of Siena at 1 site in Italy.
Trial summary
Intravenous loop diuretics is the therapy most commonly used to treat pulmonary congestion and systemic fluid overload. In theory, continuous infusion should allow for a more consistent diuresis, avoiding the sodium reabsorption in the distal tubule as well as the neurohormonal activation. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Acute Heart Failure
- What is being tested?
- furosemide infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteItaly
- Study dates
- Apr 2010to 28 Dec 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients took part in the random sample selection if they met the diagnostic criteria for acute decompensated HF.
- Patients with primary diagnosis of ADHF, volume overload with cardia dilation and LVEF <50%, and had BNP levels >100 pg/ml.
Who cannot join
- Patients were excluded if they had received more than 2 IV doses of furosemide or any continuous infusion of furosemide 1 month before randomization
- If they had end-stage renal disease or the need for renal replacement therapy, isolated diastolic dysfunction.
- Recent myocardial infarction
Trial locations and contacts
1 site in 1 country.
Italy1 site
Department of Internal Medicine, Cardiology Section Center
Siena, 53100
About this study
Official title: Continuous Versus Intermittent Loop Diuretics Infusion Dosing in Acute Heart Failure: Effects on Renal Function, Outcome and BNP Levels
Intravenous loop diuretics is the therapy most commonly used to treat pulmonary congestion and systemic fluid overload. In theory, continuous infusion should allow for a more consistent diuresis, avoiding the sodium reabsorption in the distal tubule as well as the neurohormonal activation. This should lead to renal function improvement and BNP decrease.
Read the detailed description
Patients were eligible if they were admitted with a primary diagnosis of ADHF, randomized within 12 h after hospital presentation, and with evidence of volume overload (pulmonary congestion) on a chest X-ray study and had BNP levels >100 pg/ml. Patients also displayed mild to moderate renal dysfunction with creatinine values up to 1.4 mg/dl. Some patients were supported with non invasive ventilation before randomization. Once the initial 12 h dose was determined, patients were randomized using a 1:1 ratio using a computer-generated scheme to receive the furosemide dose either divided into a twice-daily bolus injection or in a continuous infusion (mixed as a 1:1 ratio in 5 % dextrose in water) for a time period ranging from 72 to 120 h. The randomization was casual, and the physicians did not previously know the assigned arm. The dose escalation and subsequent titration of furosemide was guided by clinical response in terms of urine output volume and body weight reduction .Before randomization, renal function parameters and BNP levels were measured in all patients. Subsequent titration of the furosemide dosage was at the discretion of the attending physician, but was guided by a dose-escalation algorithm based on the treatment response (weight loss and urine output volume), symptom improvement, changes in renal function, electrolyte balance, and chest radiography. The specific doses of furosemide and the use of additional agents to manage ADHF (dopamine, IV vasodilators, hypertonic saline infusion) were decided based upon blood pressure measurements, renal function evaluation and diuresis response. Supplementary treatment was left to the discretion of the treating physician. The duration of infusion was continued for up to 72 h, at 48 h the physicians had the possibility to adjust diuretic dose administration on the basis of the clinical response. After 72 h the treatment could be stopped or continued for an additional 36-48 h depending on the patient's condition and diuresis response. Acute kidney injury (AKI) was defined following the RIFLE criteria.
Abbreviations:
(AKI) Acute kidney injury (ADHF) Acute decompensated heart failure (BNP) B-type natriuretic peptide (CHD) Coronary heart disease (cIV) Continuous infusion (iIV) Intermittent infusione (eGFR)Estimated glomerular filtration rate (Hb) Hemoglobin (HF) Heart failure (Hct) Hematocrit (LVEF) Left ventricular ejection fraction (RBC) Red blood cells
- Conditions
- Acute Heart Failure
- Being tested
- furosemide infusion
- Keywords
- acute heart failure, diuretics, BNP, Renal function, acute decompensated Heart Failure,, volume overload
- Medical subject headings
- Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
furosemide infusionDrug
Also called Continuous vs intermittent intravenous furosemide infusion
Patients were randomized in a 1:1 ratio to receive furosemide dose divided into twice-daily bolus injection (group 0) or continuous infusion (group 1)(mixed as a 1:1 ratio in 5% dextrose in water) for a time period ranging from 72 to 120 hours. The mean daily diuretic dosage was similar in the two groups. The median time from presentation to randomization was 16 hours, and the median duration of study-drug administration was 112± 24 hours
| Study group | Role | What they receive |
|---|---|---|
| Continuous furosemide infusion | Experimental | The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients; Receives: Drug: furosemide infusion |
| Intermittent furosemide infusion | Experimental | The group that received the bolus infusion of furosemide (iIV), consisted of 27 patients Receives: Drug: furosemide infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of Mean Urine Output Volume During the Infusion Period
this study aimed to evaluate the effects of continuous infusion of furosemide in comparison to twice daily regimens at similar doses with respect to changes in renal function in terms of creatinine levels and GFR, urine output and BNP levels from admission to discharge
Measured: time period ranging from 72 h to 120 h.
Evaluation of Renal Function in Terms of Creatinine Levels at Discharge
Measured: from admission to discharge, an average of 12 days
Evaluation of Renal Function in Terms of Changes in Creatinine Levels
evaluation of renal function in terms of changes in creatinine levels during hospitalization in the two arms.
Measured: participants were followed for the duration of hospital stay, an average of 13 days
Evaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment
Measured: from admission to discharge, an average of 12 days
Change in Brain Natriuretic Peptide (BNP) Levels From Admission to the Discharge
Measured: participants were followed for the duration of hospital stay, an average of 13 days
Evaluation of Renal Function in Terms of Changes in GFR
Measured: from admission to discharge, an average of 12 days
Evaluation of Renal Function in Terms of GFR Values at Discharge
Measured: from admission to discharge, an average of 12 days
Secondary outcomes (2)
Length of Hospitalization in the Two Groups
percentage of participants with hospital stay > 10 days
Measured: in-hospital
Dopamine Infusion During Hospitalization
Measured: in-hospital
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2011 (estimated)
- Study startApr 2010
- Primary completionJun 2016
- Study completion28 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Acute Heart FailureStudies 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
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Siena
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alberto Palazzuoli MD PhD, University of Siena
- Investigators
- Alberto Palazzuoli, MD, Principal investigator, Department of Internal Medicine, Cardiology Unit, Le Scotte Hospital, Siena
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01441245
- Sponsor's protocol ID
- diuretic1
- Acronym
- diurHF
- Status last verified
- Dec 2017
- First submitted
- 22 Sep 2011
- Last updated
- 23 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Palazzuoli A, Pellegrini M, Franci B, Beltrami M, Ruocco G, Gonnelli S, Angelini GD, Nuti R. Short and long-term effects of continuous versus intermittent loop diuretics treatment in acute heart failure with renal dysfunction. Intern Emerg Med. 2015 Feb;10(1):41-9. doi: 10.1007/s11739-014-1112-5. Epub 2014 Aug 3.
PubMed 25087085Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805. doi: 10.1056/NEJMoa1005419.
PubMed 21366472Ruocco G, Feola M, Nuti R, Luschi L, Evangelista I, Palazzuoli A. Loop Diuretic Administration in Patients with Acute Heart Failure and Reduced Systolic Function: Effects of Different Intravenous Diuretic Doses and Diuretic Response Measurements. J Clin Med. 2019 Nov 2;8(11):1854. doi: 10.3390/jcm8111854.
PubMed 31684094Ruocco G, Evangelista I, Franci B, Lucani B, Martini S, Nuti R, Palazzuoli A. Combination of ST2 and B-type natriuretic peptide in diabetic patients with acute heart failure: relation with ventricular stiffness and outcome. J Cardiovasc Med (Hagerstown). 2019 Feb;20(2):81-90. doi: 10.2459/JCM.0000000000000741.
PubMed 30540645Palazzuoli A, Pellegrini M, Ruocco G, Martini G, Franci B, Campagna MS, Gilleman M, Nuti R, McCullough PA, Ronco C. Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial. Crit Care. 2014 Jun 28;18(3):R134. doi: 10.1186/cc13952.
PubMed 24974232
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Continuous Versus Intermittent Loop Diuretics Infusion Dosing in Acute Heart Failure: Effects on Renal Function, Outcome and BNP Levels
- ClinicalTrials.gov ID
- NCT01441245
- Acronym / sponsor ID
- diurHF / diuretic1
- Conditions
- Acute Heart Failure
- Keywords
- acute heart failure, diuretics, BNP, Renal function, acute decompensated Heart Failure,, volume overload
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- University of SienaUniversity, hospital or other
- Study start
- Apr 2010 (actual)
- Primary completion
- Jun 2016 (actual)
- Study completion
- 28 Dec 2017 (actual)
- First posted
- 27 Sep 2011 (estimated)
- Results
- Posted 2 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Intravenous loop diuretics is the therapy most commonly used to treat pulmonary congestion and systemic fluid overload. In theory, continuous infusion should allow for a more consistent diuresis, avoiding the sodium reabsorption in the distal tubule as well as the neurohormonal activation. This should lead to renal function improvement and BNP decrease.
Detailed description
Patients were eligible if they were admitted with a primary diagnosis of ADHF, randomized within 12 h after hospital presentation, and with evidence of volume overload (pulmonary congestion) on a chest X-ray study and had BNP levels >100 pg/ml. Patients also displayed mild to moderate renal dysfunction with creatinine values up to 1.4 mg/dl. Some patients were supported with non invasive ventilation before randomization. Once the initial 12 h dose was determined, patients were randomized using a 1:1 ratio using a computer-generated scheme to receive the furosemide dose either divided into a twice-daily bolus injection or in a continuous infusion (mixed as a 1:1 ratio in 5 % dextrose in water) for a time period ranging from 72 to 120 h. The randomization was casual, and the physicians did not previously know the assigned arm. The dose escalation and subsequent titration of furosemide was guided by clinical response in terms of urine output volume and body weight reduction .Before randomization, renal function parameters and BNP levels were measured in all patients. Subsequent titration of the furosemide dosage was at the discretion of the attending physician, but was guided by a dose-escalation algorithm based on the treatment response (weight loss and urine output volume), symptom improvement, changes in renal function, electrolyte balance, and chest radiography. The specific doses of furosemide and the use of additional agents to manage ADHF (dopamine, IV vasodilators, hypertonic saline infusion) were decided based upon blood pressure measurements, renal function evaluation and diuresis response. Supplementary treatment was left to the discretion of the treating physician. The duration of infusion was continued for up to 72 h, at 48 h the physicians had the possibility to adjust diuretic dose administration on the basis of the clinical response. After 72 h the treatment could be stopped or continued for an additional 36-48 h depending on the patient's condition and diuresis response. Acute kidney injury (AKI) was defined following the RIFLE criteria.
Abbreviations:
(AKI) Acute kidney injury (ADHF) Acute decompensated heart failure (BNP) B-type natriuretic peptide (CHD) Coronary heart disease (cIV) Continuous infusion (iIV) Intermittent infusione (eGFR)Estimated glomerular filtration rate (Hb) Hemoglobin (HF) Heart failure (Hct) Hematocrit (LVEF) Left ventricular ejection fraction (RBC) Red blood cells
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Continuous furosemide infusion | Experimental | Drug: furosemide infusionThe group that received the continuous infusion of furosemide (cIV), consisted of 30 patients; |
| Intermittent furosemide infusion | Experimental | Drug: furosemide infusionThe group that received the bolus infusion of furosemide (iIV), consisted of 27 patients |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients took part in the random sample selection if they met the diagnostic criteria for acute decompensated HF.
- Patients with primary diagnosis of ADHF, volume overload with cardia dilation and LVEF <50%, and had BNP levels >100 pg/ml.
Key exclusion criteria (3 listed)
- Patients were excluded if they had received more than 2 IV doses of furosemide or any continuous infusion of furosemide 1 month before randomization
- If they had end-stage renal disease or the need for renal replacement therapy, isolated diastolic dysfunction.
- Recent myocardial infarction
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 |
|---|---|---|
| furosemide infusionAlso: Continuous vs intermittent intravenous furosemide infusionPatients were randomized in a 1:1 ratio to receive furosemide dose divided into twice-daily bolus injection (group 0) or continuous infusion (group 1)(mixed as a 1:1 ratio in 5% dextrose in water) for a time period ranging from 72 to 120 hours. The mean daily diuretic dosage was similar in the two groups. The median time from presentation to randomization was 16 hours, and the median duration of study-drug administration was 112± 24 hours | Drug | Continuous furosemide infusion, Intermittent furosemide infusion |
Primary outcome
Evaluation of Mean Urine Output Volume During the Infusion Period
Time frame: time period ranging from 72 h to 120 h.
this study aimed to evaluate the effects of continuous infusion of furosemide in comparison to twice daily regimens at similar doses with respect to changes in renal function in terms of creatinine levels and GFR, urine output and BNP levels from admission to discharge
Evaluation of Renal Function in Terms of Creatinine Levels at Discharge
Time frame: from admission to discharge, an average of 12 days
Evaluation of Renal Function in Terms of Changes in Creatinine Levels
Time frame: participants were followed for the duration of hospital stay, an average of 13 days
evaluation of renal function in terms of changes in creatinine levels during hospitalization in the two arms.
Evaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment
Time frame: from admission to discharge, an average of 12 days
Change in Brain Natriuretic Peptide (BNP) Levels From Admission to the Discharge
Time frame: participants were followed for the duration of hospital stay, an average of 13 days
Evaluation of Renal Function in Terms of Changes in GFR
Time frame: from admission to discharge, an average of 12 days
Evaluation of Renal Function in Terms of GFR Values at Discharge
Time frame: from admission to discharge, an average of 12 days
2 secondary outcomes
Length of Hospitalization in the Two Groups
Time frame: in-hospital
Dopamine Infusion During Hospitalization
Time frame: in-hospital
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25087085Palazzuoli A, Pellegrini M, Franci B, Beltrami M, Ruocco G, Gonnelli S, Angelini GD, Nuti R. Short and long-term effects of continuous versus intermittent loop diuretics treatment in acute heart failure with renal dysfunction. Intern Emerg Med. 2015 Feb;10(1):41-9. doi: 10.1007/s11739-014-1112-5. Epub 2014 Aug 3.
- Results publication: PubMed 21366472Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805. doi: 10.1056/NEJMoa1005419.
- Derived from this study: PubMed 31684094Ruocco G, Feola M, Nuti R, Luschi L, Evangelista I, Palazzuoli A. Loop Diuretic Administration in Patients with Acute Heart Failure and Reduced Systolic Function: Effects of Different Intravenous Diuretic Doses and Diuretic Response Measurements. J Clin Med. 2019 Nov 2;8(11):1854. doi: 10.3390/jcm8111854.
- Derived from this study: PubMed 30540645Ruocco G, Evangelista I, Franci B, Lucani B, Martini S, Nuti R, Palazzuoli A. Combination of ST2 and B-type natriuretic peptide in diabetic patients with acute heart failure: relation with ventricular stiffness and outcome. J Cardiovasc Med (Hagerstown). 2019 Feb;20(2):81-90. doi: 10.2459/JCM.0000000000000741.
- Derived from this study: PubMed 24974232Palazzuoli A, Pellegrini M, Ruocco G, Martini G, Franci B, Campagna MS, Gilleman M, Nuti R, McCullough PA, Ronco C. Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial. Crit Care. 2014 Jun 28;18(3):R134. doi: 10.1186/cc13952.
- Individual participant dataSharing planned: No
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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.
Alberto Palazzuoli, MD principal investigator
Department of Internal Medicine, Cardiology Unit, Le Scotte Hospital, Siena
1 site 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 infusion in people with Acute Heart Failure, run by University of Siena at 1 site 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 2 inclusion and 3 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 23 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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?
Yes. Results are posted in the registry (first posted 2 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Evaluation of Mean Urine Output Volume During the Infusion Period (time frame: time period ranging from 72 h to 120 h.). The study lists 7 primary outcomes in all. 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 NCT01441245, which also lists 5 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 23 Jan 2018.