Acute Decompensated Heart FailurePhase 4COMBIND-HFNCT05840536
Combination Diuretic Therapy for Acute Decompensated Heart Failure
A Phase 4 study testing Furosemide plus Chlorothiazide and Furosemide in people with Acute Decompensated Heart Failure, run by Ochsner Health System at 1 site in United States.
Trial summary
Patients with heart failure are often admitted to the hospital because they have accumulated excessive amounts of fluid, they become short of breath and congested with fluid. Removing the excess fluid is necessary to improve the patients symptoms and reduce the risk of being re-admitted to the hospital. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Acute Decompensated Heart Failure
- What is being tested?
- Furosemide plus Chlorothiazide and Furosemide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to Oct 2015
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of Acute Decompensated Heart Failure - by at least 1 symptom (dyspnea, exercise intolerance, weight gain, edema) and at least 1 sign (chest x-ray (CXR), elevated brain natriuretic peptide (BNP), rales, elevated jugular venous pressure (JVP)).
- History of Congestion Heart Failure (CHF) with chronic loop diuretic use for at least the past 4 weeks
- Echocardiogram in the past 12 months (to document Ejection fraction (EF))
Who cannot join
- Chronic Kidney Disease (CKD) or Acute Kidney Injury (AKI) - Cr >2.5 mg/dL
- Ventricular assist device
- Cardiogenic shock
- Need for mechanical or vasopressor support on admission
- Significant co-morbidities: Chronic Obstructive Pulmonary Disease, pneumonia, pulmonary embolism
- History of pulmonary hypertension (PAH) (World Health Organization (WHO) group I primary PAH)
- Acute Ischemia / post-intervention (Coronary Artery Bypass Graft, Percutaneous Coronary Interventions) in the past 90 days
Trial locations and contacts
1 site in 1 country.
United States1 site
Ochsner Heart and Vascular Institute
New Orleans, Louisiana, 70121
About this study
Official title: Efficacy and Tolerability of Combination Intravenous Diuretic Therapy Versus Intravenous Loop Diuretic Therapy Alone for the Treatment of Acute Decompensated Heart Failure
Patients with heart failure are often admitted to the hospital because they have accumulated excessive amounts of fluid, they become short of breath and congested with fluid. Removing the excess fluid is necessary to improve the patients symptoms and reduce the risk of being re-admitted to the hospital. Diuretics ("water pills") are often given through an IV to accelerate the fluid removal. Furosemide is commonly used for fluid removal, however some patients do not respond well to the medication. There are other diuretics available that can work in conjunction with furosemide and increase the rate of fluid removal. The other "water pills" have slightly different mechanisms of action in the body compared to furosemide and when combined they may increase fluid removal.
The investigators hypothesize that adding chlorothiazide to furosemide will result in quicker and more effective fluid removal in heart failure patients.
Read the detailed description
The investigators will randomly assign patients to receive either furosemide alone or furosemide in combination with chlorothiazide when they are admitted to the hospital with acute heart failure and excessive volume.
All patients will be monitored for rate of fluid removal, improvement in symptoms, and side-effects of the medications.
- Conditions
- Acute Decompensated Heart Failure
- Being tested
- Furosemide plus Chlorothiazide, Furosemide
- Keywords
- heart failure, acute, diuretic, management, renal function, chlorothiazide, furosemide
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Furosemide plus ChlorothiazideDrug
Also called Lasix plus Diuril
Patients will receive lasix infusion starting at 5mg/hr along with a bolus dose of chlorothiazide 250mg at the initiation of the protocol. The lasix infusion can be titrated to 10mg after 12hrs based on volume of diuresis. This arm will also receive 250mg bolus doses of chlorothiazide every 12hrs for the duration of the study.
Intravenous (IV) lasix infusion at 5mg/hr plus IV boluses of diuril every 12 hrs.
FurosemideDrug
Also called Lasix
Patients will receive furosemide infusion at 5mg/hr along with an initial bolus dose of furosemide equal to twice their home oral dose. The furosemide infusion can be increased to 10mg/hr after 12hrs based on urine output. This arm will receive bolus doses of furosemide every 12hrs equal to twice their home oral dose until completion of the protocol.
| Study group | Role | What they receive |
|---|---|---|
| Combination Diuretic Therapy | Experimental | Patients will receive lasix infusion starting at 5mg/hr along with a bolus dose of chlorothiazide 250mg at the initiation of the protocol. The lasix infusion can be titrated to 10mg after 12hrs based on volume of diuresis. This arm will also receive 250mg bolus doses of chlorothiazide every 12hrs for the duration of the study. Receives: Drug: Furosemide plus Chlorothiazide; Drug: Furosemide |
| Monotherapy Diuretic | Active comparator | Patients will receive furosemide infusion at 5mg/hr along with an initial bolus dose of furosemide equal to twice their home oral dose. The furosemide infusion can be increased to 10mg/hr after 12hrs based on urine output. This arm will receive bolus doses of furosemide every 12hrs equal to twice their home oral dose until completion of the protocol. Receives: Drug: Furosemide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Volume of Diuresis
Total volume of urine output will be collected during the first 72 hours of admission.
Measured: During Index Hospitalization at 72 hours
Change in Serum Creatinine from Baseline
Change in serum creatinine from baseline after 72 hours of diuresis
Measured: During Index Admission up to 120 hours
Secondary outcomes (7)
Hypokalemia
Measured: From date of index hospitalization until 72 hours after diuresis
Electrolyte Disturbances
Magnesium, Phosphorous
Measured: From date of index hospitalization until 72 hours after diuresis
Total Weight Loss
Measured: From date of index hospitalization until 72 hours after diuresis
Relief of Symptoms
Using the five-point Likert scale for dyspnea which ranges from 1-5 where the lower the score the better the outcome
Measured: From date of index hospitalization until 72 hours after diuresis
Length of Stay
Measured: From date of index hospitalization until date of discharge from hospital, assessed up to 1 week
Potassium Replacement Requirements
Measured: From date of index hospitalization until date of discharge from hospital, assessed up to 1 week
Adverse Events
Hypotension, dizziness, syncope, acute renal failure, arrhythmia
Measured: From date of index hospitalization until date of discharge from hospital, assessed up to 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2023
- Study startMay 2014
- Primary completionOct 2015 (estimated)
- Study completionOct 2015 (estimated)
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 Acute Decompensated 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
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ochsner Health System
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Patrick T Campbell, MD, Study director, Ochsner Heart and Vascular InstituteStacy Mandras, MD, Principal investigator, Ochsner Heart and Vascular Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05840536
- Sponsor's protocol ID
- OchsnerHS
- Acronym
- COMBIND-HF
- Status last verified
- Apr 2023
- First submitted
- 22 Apr 2014
- Last updated
- 3 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Felker 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 21366472Channer KS, McLean KA, Lawson-Matthew P, Richardson M. Combination diuretic treatment in severe heart failure: a randomised controlled trial. Br Heart J. 1994 Feb;71(2):146-50. doi: 10.1136/hrt.71.2.146.
PubMed 8130022Peacock WF, Costanzo MR, De Marco T, Lopatin M, Wynne J, Mills RM, Emerman CL; ADHERE Scientific Advisory Committee and Investigators. Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry. Cardiology. 2009;113(1):12-9. doi: 10.1159/000164149. Epub 2008 Oct 17.
PubMed 18931492
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Tolerability of Combination Intravenous Diuretic Therapy Versus Intravenous Loop Diuretic Therapy Alone for the Treatment of Acute Decompensated Heart Failure
- ClinicalTrials.gov ID
- NCT05840536
- Acronym / sponsor ID
- COMBIND-HF / OchsnerHS
- Conditions
- Acute Decompensated Heart Failure
- Keywords
- heart failure, acute, diuretic, management, renal function, chlorothiazide, furosemide
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Ochsner Health SystemUniversity, hospital or other
- Study start
- May 2014
- Primary completion
- Oct 2015 (estimated)
- Study completion
- Oct 2015 (estimated)
- First posted
- 3 May 2023 (actual)
- 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.
Patients with heart failure are often admitted to the hospital because they have accumulated excessive amounts of fluid, they become short of breath and congested with fluid. Removing the excess fluid is necessary to improve the patients symptoms and reduce the risk of being re-admitted to the hospital. Diuretics ("water pills") are often given through an IV to accelerate the fluid removal. Furosemide is commonly used for fluid removal, however some patients do not respond well to the medication. There are other diuretics available that can work in conjunction with furosemide and increase the rate of fluid removal. The other "water pills" have slightly different mechanisms of action in the body compared to furosemide and when combined they may increase fluid removal.
The investigators hypothesize that adding chlorothiazide to furosemide will result in quicker and more effective fluid removal in heart failure patients.
Detailed description
The investigators will randomly assign patients to receive either furosemide alone or furosemide in combination with chlorothiazide when they are admitted to the hospital with acute heart failure and excessive volume.
All patients will be monitored for rate of fluid removal, improvement in symptoms, and side-effects of the medications.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Combination Diuretic Therapy | Experimental | Drug: Furosemide plus Chlorothiazide, Drug: FurosemidePatients will receive lasix infusion starting at 5mg/hr along with a bolus dose of chlorothiazide 250mg at the initiation of the protocol. The lasix infusion can be titrated to 10mg after 12hrs based on volume of diuresis. This arm will also receive 250mg bolus doses of chlorothiazide every 12hrs for the duration of the study. |
| Monotherapy Diuretic | Active comparator | Drug: FurosemidePatients will receive furosemide infusion at 5mg/hr along with an initial bolus dose of furosemide equal to twice their home oral dose. The furosemide infusion can be increased to 10mg/hr after 12hrs based on urine output. This arm will receive bolus doses of furosemide every 12hrs equal to twice their home oral dose until completion of the protocol. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of Acute Decompensated Heart Failure - by at least 1 symptom (dyspnea, exercise intolerance, weight gain, edema) and at least 1 sign (chest x-ray (CXR), elevated brain natriuretic peptide (BNP), rales, elevated jugular venous pressure (JVP)).
- History of Congestion Heart Failure (CHF) with chronic loop diuretic use for at least the past 4 weeks
- Echocardiogram in the past 12 months (to document Ejection fraction (EF))
Key exclusion criteria (7 listed)
- Chronic Kidney Disease (CKD) or Acute Kidney Injury (AKI) - Cr >2.5 mg/dL
- Ventricular assist device
- Cardiogenic shock
- Need for mechanical or vasopressor support on admission
- Significant co-morbidities: Chronic Obstructive Pulmonary Disease, pneumonia, pulmonary embolism
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 plus ChlorothiazideAlso: Lasix plus DiurilPatients will receive lasix infusion starting at 5mg/hr along with a bolus dose of chlorothiazide 250mg at the initiation of the protocol. The lasix infusion can be titrated to 10mg after 12hrs based on volume of diuresis. This arm will also receive 250mg bolus doses of chlorothiazide every 12hrs for the duration of the study. Intravenous (IV) lasix infusion at 5mg/hr plus IV boluses of diuril every 12 hrs. | Drug | Combination Diuretic Therapy |
| FurosemideAlso: LasixPatients will receive furosemide infusion at 5mg/hr along with an initial bolus dose of furosemide equal to twice their home oral dose. The furosemide infusion can be increased to 10mg/hr after 12hrs based on urine output. This arm will receive bolus doses of furosemide every 12hrs equal to twice their home oral dose until completion of the protocol. | Drug | Combination Diuretic Therapy, Monotherapy Diuretic |
Primary outcome
Volume of Diuresis
Time frame: During Index Hospitalization at 72 hours
Total volume of urine output will be collected during the first 72 hours of admission.
Change in Serum Creatinine from Baseline
Time frame: During Index Admission up to 120 hours
Change in serum creatinine from baseline after 72 hours of diuresis
7 secondary outcomes
Hypokalemia
Time frame: From date of index hospitalization until 72 hours after diuresis
Electrolyte Disturbances
Time frame: From date of index hospitalization until 72 hours after diuresis
Total Weight Loss
Time frame: From date of index hospitalization until 72 hours after diuresis
Relief of Symptoms
Time frame: From date of index hospitalization until 72 hours after diuresis
Length of Stay
Time frame: From date of index hospitalization until date of discharge from hospital, assessed up to 1 week
Potassium Replacement Requirements
Time frame: From date of index hospitalization until date of discharge from hospital, assessed up to 1 week
Adverse Events
Time frame: From date of index hospitalization until date of discharge from hospital, assessed up to 1 week
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Background: 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.
- Background: PubMed 8130022Channer KS, McLean KA, Lawson-Matthew P, Richardson M. Combination diuretic treatment in severe heart failure: a randomised controlled trial. Br Heart J. 1994 Feb;71(2):146-50. doi: 10.1136/hrt.71.2.146.
- Background: PubMed 18931492Peacock WF, Costanzo MR, De Marco T, Lopatin M, Wynne J, Mills RM, Emerman CL; ADHERE Scientific Advisory Committee and Investigators. Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry. Cardiology. 2009;113(1):12-9. doi: 10.1159/000164149. Epub 2008 Oct 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.
Patrick T Campbell, MD study director
Ochsner Heart and Vascular Institute
Stacy Mandras, MD principal investigator
Ochsner Heart and Vascular Institute
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 plus Chlorothiazide and Furosemide in people with Acute Decompensated Heart Failure, run by Ochsner Health System at 1 site in United States.
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 3 inclusion and 7 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: withdrawn, as of the sponsor's last update on 3 May 2023. 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 United States. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Volume of Diuresis (time frame: During Index Hospitalization at 72 hours). The study lists 2 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 NCT05840536, 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 3 May 2023.