Acute Decompensated Heart FailurePhase 1/2DIVERSION-HFNCT02721511
A Study to Investigate the Safety and Efficacy of a Novel Furosemide Regimen
A Phase 1/2 study testing Furosemide Injection Solution 8mg/mL in people with Acute Decompensated Heart Failure, run by Todd M Koelling, MD at 1 site in United States.
Trial summary
This is a, prospective, single center, open-label, pilot study to evaluate the safety and efficacy of the subcutaneous administration of a novel furosemide formulation. The results of this pilot study will be reviewed to determine the safety of the subcutaneous treatment regimen and to evaluate patient selection… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Decompensated Heart Failure
- What is being tested?
- Furosemide Injection Solution 8mg/mL
- Type of treatment
- 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 2016to 7 Mar 2017
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female or male 18 years or older
- History of heart failure >90-days
- Presenting to the University of Michigan Health System because of evidence of fluid overload and recommended for admission or observation unit stay to receive intravenous (IV) furosemide therapy.
- Estimated excess fluid weight of 10 lbs or more from euvolemic state.
- Estimated jugular venous pressure (JVP) ≥ 10 cm above the right atrium (RA).
- Evidence of edema up to mid shin or higher
- Agreeing to sign informed consent and HIPAA authorization
- Daily dose of furosemide prescribed ≤ 160 mg, or torsemide ≤ 40 mg or bumetanide ≤ 4 mg.
Who cannot join
- Pregnant females or women of child-bearing age who are not willing to use an adequate form of contraception
- Chronic Obstructive Pulmonary Disease (COPD) moderate or worse: FEV1/FCV ratio <0.7 and FEV1 <60 percent predicted.
- Rapid atrial fibrillation (AF) (HR >100b/min)
- Hypoxia (resting O2 saturation <9%)
- Hypotension (systolic blood pressure (SBP) BP < 90 mmHg)
- Uncontrolled diabetes mellitus (DM) (admission glucose levels > 300 mg/dL)
Show all 12Show fewer
- Advanced renal disease (eGFR < 30mL/min/1.73m2)
- Hypoalbuminemia (Albumin < 3.0 g/dL)
- Acute coronary syndrome
- Serum potassium (K+) <3.5 meq/L or using potassium supplements equivalent to > 80meq/day.
- 13. On experimental medication or currently participating in cardiovascular research study.
- 14. Urinary tract abnormality or disorder interfering with urination. 15. Allergy to the active and inactive ingredients of the study medication. 16. Inability to comply with study requirements 17. Dementia 18. Ongoing substance abuse
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Health System
Ann Arbor, Michigan, 48109
About this study
Official title: A Pilot Study to Investigate the Safety and Efficacy of a Novel Furosemide Regimen, Administered Subcutaneously for the Treatment of Fluid Overload and to Evaluate the Feasibility for Home Treatment
This is a, prospective, single center, open-label, pilot study to evaluate the safety and efficacy of the subcutaneous administration of a novel furosemide formulation. The results of this pilot study will be reviewed to determine the safety of the subcutaneous treatment regimen and to evaluate patient selection criteria for possible at home treatment. The intent is to conduct a future follow on study looking at the feasibility of at home treatment of patients referred to a hospital for treatment of fluid overload.
Read the detailed description
In this pilot study, the treatment in the hospital setting will simulate how the patient would be treated at home in the feasibility study. The results of this pilot will be used to inform the design of the feasibility study. The future feasibility study will test the concept that removing the need for professional care for furosemide administration allows a proportion of these patients to go home and be treated safely at home.
A total of 10 patients will be studied using an open label approach to assess efficacy, tolerability and safety of subcutaneous administration of a novel furosemide regimen, administered subcutaneously.
Patients who are referred to the hospital for treatment of fluid overload will complete screening and treatment phases. Subjects meeting the eligibility criteria will be administered a test dose of 80mg furosemide USP administered by intravenous (IV) bolus over 2 minutes. Fluid intake will be restricted during the 2-hour observation period.
Only patients who respond to the test dose of commercially available 80mg intravenous (IV) furosemide (alternatively, bumetanide 2 mg IV ) by means of diuresis in excess of 400 mL over 2 hours will be eligible to enter the treatment phase of the study with the Investigational Medicinal Product. Patients who have responded to the equivalent dose of furosemide or bumetanide as part of their clinical care for heart failure in the hospital within 24 hours of recruitment will not require this test dose and will be eligible for entry into the study provided they meet all of the entry criteria for the study.
Non-responders will be treated in the hospital with usual care.
Investigational Medicinal Product:
Subjects who are Diuretic Responders will be treated with the Investigational Medicinal Product for a period of 24 hours. Furosemide Injection Solution, 8 mg/mL (80 mg total dose) will be administered subcutaneously by means of the B. Braun Perfusor® Space Infusion Pump System. The pump will be programmed to deliver 80mg of furosemide over 5 hours with 30mg administered during the first hour followed by 12.5mg/hour for 4 hours.
Subjects will be treated with twice daily dosing, by default, but may be reduced to once daily if it is desired to reduce the daily urine response. The duration and frequency of the treatment will be determined by the attending cardiologist.
If the subject requires further diuresis after 24 hours, they will be converted to usual care at that time. If the attending cardiologist makes the determination at any time that the diuresis is not adequate, the subject's participation in the study will be stopped, and the patient will convert over to usual care.
Urine output every 24 hours will be recorded, as will daily weights. Serum potassium, sodium, blood urea nitrogen, creatinine and hemoglobin will be assessed daily. All patients will be monitored for heart rhythm continuously during the hospitalization. Temperature every 8 hours will be recorded, and the injection site will be assessed daily for signs of erythema.
- Conditions
- Acute Decompensated Heart Failure
- Being tested
- Furosemide Injection Solution 8mg/mL
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Furosemide Injection Solution 8mg/mLDrug
Also called SCP-101, Buffered Lasix, Buffered furosemide
Furosemide Injection Solution, 8 mg/mL, (total dose =80 mg) administered subcutaneously as 30 mg over the first hour and then as 12.5 mg per hour over the subsequent 4 hours by means of the B. Braun Perfusor® Space Infusion Pump System.
| Study group | Role | What they receive |
|---|---|---|
| Furosemide injection solution 8mg/mL | Experimental | 8mg/mL (total dose=80mg) of furosemide injection solution administered subcutaneously as 30mg over the first hour and then as 12.5 mg per hours over the subsequent 4 hours. Receives: Drug: Furosemide Injection Solution 8mg/mL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy endpoint: Urine output per 24 hours
Efficacy will be measured as the ability of the diuretic regimen given one or two times daily to achieve a net 24 hour urine output of 3000 cc or more over the first 24 hours of the study.
Measured: 24 hours
Safety endpoint: Composite of Severe hypokalemia, severe hyperkalemia, moderate to severe worsening of renal function, fever, sepsis, intravenous catheter infection, cardiac dysrhythmia causing syncope or requiring therapy or death
Safety will be assessed as the composite of developing any of the pre-specified serious adverse events: Severe hypokalemia, severe hyperkalemia, moderate to severe worsening of renal function, fever, sepsis, intravenous catheter infection, cardiac dysrhythmia causing syncope or requiring therapy, death.
Measured: 24 hours
Secondary outcomes (4)
Functional Status
New York Heart Association class
Measured: 24 hours
Quality of life
Kansas City Cardiomyopathy Questionnaire
Measured: 24 hours
Congestion Scale
Change in congestion scale
Measured: 24 hours
Breathlessness
Visual analog scale for dyspnea
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2016 (estimated)
- Study startMay 2016
- Primary completion7 Mar 2017
- Study completion7 Mar 2017
Why it stopped: Investigator decision based on new device information.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Todd M Koelling, MD
- Sponsor type
- University, hospital or other
- Collaborators
- scPharmaceuticals, Inc.
- Responsible party
- Sponsor-investigator, Todd M Koelling, MD, University of Michigan
- Investigators
- Todd M Koelling, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02721511
- Sponsor's protocol ID
- HUM00107057
- Acronym
- DIVERSION-HF
- Status last verified
- Mar 2017
- First submitted
- 17 Mar 2016
- Last updated
- 24 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Investigate the Safety and Efficacy of a Novel Furosemide Regimen, Administered Subcutaneously for the Treatment of Fluid Overload and to Evaluate the Feasibility for Home Treatment
- ClinicalTrials.gov ID
- NCT02721511
- Acronym / sponsor ID
- DIVERSION-HF / HUM00107057
- Conditions
- Acute Decompensated Heart Failure
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Investigator decision based on new device information.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Todd M Koelling, MDUniversity, hospital or other
- Collaborators
- scPharmaceuticals, Inc.
- Study start
- May 2016 (actual)
- Primary completion
- 7 Mar 2017 (actual)
- Study completion
- 7 Mar 2017 (actual)
- First posted
- 29 Mar 2016 (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.
This is a, prospective, single center, open-label, pilot study to evaluate the safety and efficacy of the subcutaneous administration of a novel furosemide formulation. The results of this pilot study will be reviewed to determine the safety of the subcutaneous treatment regimen and to evaluate patient selection criteria for possible at home treatment. The intent is to conduct a future follow on study looking at the feasibility of at home treatment of patients referred to a hospital for treatment of fluid overload.
Detailed description
In this pilot study, the treatment in the hospital setting will simulate how the patient would be treated at home in the feasibility study. The results of this pilot will be used to inform the design of the feasibility study. The future feasibility study will test the concept that removing the need for professional care for furosemide administration allows a proportion of these patients to go home and be treated safely at home.
A total of 10 patients will be studied using an open label approach to assess efficacy, tolerability and safety of subcutaneous administration of a novel furosemide regimen, administered subcutaneously.
Patients who are referred to the hospital for treatment of fluid overload will complete screening and treatment phases. Subjects meeting the eligibility criteria will be administered a test dose of 80mg furosemide USP administered by intravenous (IV) bolus over 2 minutes. Fluid intake will be restricted during the 2-hour observation period.
Only patients who respond to the test dose of commercially available 80mg intravenous (IV) furosemide (alternatively, bumetanide 2 mg IV ) by means of diuresis in excess of 400 mL over 2 hours will be eligible to enter the treatment phase of the study with the Investigational Medicinal Product. Patients who have responded to the equivalent dose of furosemide or bumetanide as part of their clinical care for heart failure in the hospital within 24 hours of recruitment will not require this test dose and will be eligible for entry into the study provided they meet all of the entry criteria for the study.
Non-responders will be treated in the hospital with usual care.
Investigational Medicinal Product:
Subjects who are Diuretic Responders will be treated with the Investigational Medicinal Product for a period of 24 hours. Furosemide Injection Solution, 8 mg/mL (80 mg total dose) will be administered subcutaneously by means of the B. Braun Perfusor® Space Infusion Pump System. The pump will be programmed to deliver 80mg of furosemide over 5 hours with 30mg administered during the first hour followed by 12.5mg/hour for 4 hours.
Subjects will be treated with twice daily dosing, by default, but may be reduced to once daily if it is desired to reduce the daily urine response. The duration and frequency of the treatment will be determined by the attending cardiologist.
If the subject requires further diuresis after 24 hours, they will be converted to usual care at that time. If the attending cardiologist makes the determination at any time that the diuresis is not adequate, the subject's participation in the study will be stopped, and the patient will convert over to usual care.
Urine output every 24 hours will be recorded, as will daily weights. Serum potassium, sodium, blood urea nitrogen, creatinine and hemoglobin will be assessed daily. All patients will be monitored for heart rhythm continuously during the hospitalization. Temperature every 8 hours will be recorded, and the injection site will be assessed daily for signs of erythema.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Furosemide injection solution 8mg/mL | Experimental | Drug: Furosemide Injection Solution 8mg/mL8mg/mL (total dose=80mg) of furosemide injection solution administered subcutaneously as 30mg over the first hour and then as 12.5 mg per hours over the subsequent 4 hours. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Female or male 18 years or older
- History of heart failure >90-days
- Presenting to the University of Michigan Health System because of evidence of fluid overload and recommended for admission or observation unit stay to receive intravenous (IV) furosemide therapy.
- Estimated excess fluid weight of 10 lbs or more from euvolemic state.
- Estimated jugular venous pressure (JVP) ≥ 10 cm above the right atrium (RA).
Key exclusion criteria (12 listed)
- Pregnant females or women of child-bearing age who are not willing to use an adequate form of contraception
- Chronic Obstructive Pulmonary Disease (COPD) moderate or worse: FEV1/FCV ratio <0.7 and FEV1 <60 percent predicted.
- Rapid atrial fibrillation (AF) (HR >100b/min)
- Hypoxia (resting O2 saturation <9%)
- Hypotension (systolic blood pressure (SBP) BP < 90 mmHg)
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 Injection Solution 8mg/mLAlso: SCP-101, Buffered Lasix, Buffered furosemideFurosemide Injection Solution, 8 mg/mL, (total dose =80 mg) administered subcutaneously as 30 mg over the first hour and then as 12.5 mg per hour over the subsequent 4 hours by means of the B. Braun Perfusor® Space Infusion Pump System. | Drug | Furosemide injection solution 8mg/mL |
Primary outcome
Efficacy endpoint: Urine output per 24 hours
Time frame: 24 hours
Efficacy will be measured as the ability of the diuretic regimen given one or two times daily to achieve a net 24 hour urine output of 3000 cc or more over the first 24 hours of the study.
Safety endpoint: Composite of Severe hypokalemia, severe hyperkalemia, moderate to severe worsening of renal function, fever, sepsis, intravenous catheter infection, cardiac dysrhythmia causing syncope or requiring therapy or death
Time frame: 24 hours
Safety will be assessed as the composite of developing any of the pre-specified serious adverse events: Severe hypokalemia, severe hyperkalemia, moderate to severe worsening of renal function, fever, sepsis, intravenous catheter infection, cardiac dysrhythmia causing syncope or requiring therapy, death.
4 secondary outcomes
Functional Status
Time frame: 24 hours
Quality of life
Time frame: 24 hours
Congestion Scale
Time frame: 24 hours
Breathlessness
Time frame: 24 hours
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 24 Mar 2017.
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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.
Todd M Koelling, MD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Furosemide Injection Solution 8mg/mL in people with Acute Decompensated Heart Failure, run by Todd M Koelling, MD 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 8 inclusion and 12 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 24 Mar 2017. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Efficacy endpoint: Urine output per 24 hours (time frame: 24 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?
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 24 Mar 2017.