The objective of this study is to prospectively compare decongestive therapy administered by the Reprieve DMS system to Optimal Diuretic Therapy (ODT) in the treatment of patients diagnosed with acute decompensated heart failure (ADHF). The main…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to compare Reprieve DMS to standard
control therapy with respect to effective decongestion and acute kidney injury
in ADHF patients.
The trial will employ co-primary endpoints, one for efficacy and one for
safety. All study endpoints will be evaluated in two study cohorts (subjects
with home dose of > 80 mg of furosemide equivalent and subjects with home dose
of <80 mg of furosemide equivalent).
Primary efficacy endpoint is total urine sodium output at 24 hours
post-treatment initiation.
Primary safety endpoint includes clinically significant acute kidney injury
defined as KDIGO stage 2 or greater AKI [>= doubling of baseline serum
creatinine or use of renal replacement therapy (RRT)], severe electrolyte
abnormality (serum potassium <3.0 mEq/L, magnesium <1.3 mEq/L or sodium <135
mEq/L*), symptomatic hypotension or hypertensive emergency.
*For subjects enrolled with baseline sodium levels of <135 mEq/L, there needs
to be drop of at least 5 mEq/L to be considered against primary safety
endpoint.
Secondary outcome
• Net fluid loss at end of randomized therapy.
• Time on IV loop diuretic Defined as the time from initiation of randomized
therapy to last dose of IV loop diuretic administered for ADHF.
The assessment of all Device and Procedure related AEs and SAEs in the study
population as determined by an Independent Clinical Events Committee (CEC), as
outlined in the committee charter. It should be noted that episodes of
hematuria associated with Foley catheter placement that can be adequately
managed will not be included as a secondary safety endpoint, since this is an
anticipated adverse event commonly associated with Foley placement.
Background summary
This study will evaluate the safety, performance, and clinical utility of the
Reprieve DMS device in comparison with *control* diuretic therapies. The
Reprieve DMS ADHF study was developed based upon the initial conclusions drawn
from the feasibility studies conducted outside the US (OUS).
The OUS feasibility studies provided the clinical experience to optimize the
Reprieve DMS system algorithm to identify and efficiently deliver an
individualized diuretic dose for each subject based upon their measured
response. Using real time information from the minute-to-minute measurement of
urine output, the system automatically identifies a target responsive diuretic
dose by sequentially increasing the rate of diuretic infusion until the patient
achieves a clinically significant rate of urine production or until a set limit
of diuretic has been infused. The system then transitions to a continuous
diuretic infusion rate based on a percentage of the amount of diuretic required
to reach the target urine output rate. The subject also receives a personalized
partial fluid/salt replacement of these urinary losses to ensure each subject
has adequate intravascular volume and avoidance of activating renal sodium
conserving pathways.
Study objective
The objective of this study is to prospectively compare decongestive therapy
administered by the Reprieve DMS system to Optimal Diuretic Therapy (ODT) in
the treatment of patients diagnosed with acute decompensated heart failure
(ADHF). The main objective is to determine if the Reprieve DMS can more
efficiently decongest ADHF patients in comparison to Control Therapy.
Study design
A prospective, multicenter, randomized, controlled pilot trial (1:1) to compare
the rate of decongestion for up to 72 hours with the Reprieve DMS compared to
optimal diuretic therapy (ODT).
Intervention
DMS Therapy
a. DMS begins by administering IV furosemide to achieve the target urine rate
of 525 ml/hr. using an exponentially increasing ramp dose until the target
urine output rate is met or maximum IV furosemide dose (200 mg) is infused
(*Dose Finding Phase*).
b. Once the target urine output rate is met, the IV furosemide infusion rate is
reduced to an hourly infusion rate that is 20% of the total furosemide dose
delivered during the Dose Finding Phase (minimum 4 mg/hr., maximum 40 mg/hr.)
to maintain effective plasma concentration of furosemide and thus maintain the
desired target urine output rate. (For example, if a total of 160 mg of
furosemide was delivered during the Dose Finding Phase, the hourly infusion
rate would be set to 32 mg/hr.).
c. The DMS provides a proportional saline replacement designed to maintain
adequate intravascular volume and prevent activation of renal sodium retaining
mechanisms. No saline is infused when the urine output rate is between 0 and
225 ml/hr. Urine output rate above this level triggers 100% IV saline
replacement to match urine output between 225 ml/hr and 425 ml/hr. For urine
output rates above 425 ml/hr to 1025 ml/hr., IV saline infusion is increased to
add a 50% match of the urine output above 425 ml/hr up to 1025 ml/hr for a
maximum infusion rate of 500 ml/hr. (Note: This saline infusion is adjusted
based on the lab urine sodium entered into the system as described below).
d. Every time the urine collection bag is emptied, a sample should be sent to
the laboratory for determination of sodium concentration. When the result is
returned from the lab, the value will be entered into the DMS by a clinical
staff member. The DMS will then calculate an *adjusted urine output rate*, and
the treatment algorithm will use this rate to determine the saline infusion
rate optimized for the patient*s urine sodium level. This process is repeated
each time the urine bag is emptied.
e. If the urine output rate meets the criteria for sustained very high urine
output rate, the DMS down-titrates the diuretic dose automatically.
f. If the patient*s urine output rate drops below the desired urine output rate
for a sustained period, the DMS provides the investigator with the option to
resume the diuretic IV furosemide Dose Finding Phase provided the previous Dose
Finding Phase did not reach the maximum dose of 200 mg.
g. If the patient*s urine output rate remains low, the DMS provides the
investigator with the option of administering additional adjunctive therapies
(i.e., thiazide/thiazide like diuretics).
Note: Subjects receiving high dose oral loop diuretic at home (> 240 mg
furosemide, 3 mg bumetanide, or 60 mg torsemide per 24 hours) must be
administered an oral long half-life thiazide/thiazide like diuretic (10mg
metolazone, 50mg chlorthalidone, 100mg HCTZ or equivalent) 2 to 12 hours prior
to initiating Reprieve therapy.
Optimal Diuretic Therapy (ODT)
Consider best practices of optimal diuretic dosing such as those demonstrated
in recent randomized trials (DOSE31, ADVOR32, CLOROTIC33). The Reprieve DMS can
infuse a maximum dose of 1,120 mg/day of furosemide. It is recommended that
subjects randomized to ODT should also not exceed maximum dose of 1,120 mg/day
of furosemide.
Note: Consideration can be given to up-front use of oral long half- thiazide
diuretic with appropriate adjustment of IV loop diuretic dose in patients
receiving high dose loop diuretic prior to enrollment (> 240 mg furosemide, 3
mg bumetanide, or 60 mg torsemide per 24 hours).
Reprieve DMS, ODT Groups
As standard background therapy, all patients must receive 2 g daily sodium diet
and a 2 L daily oral fluid intake restriction, in addition to strict fluid
input and output recording and daily weights.
Study burden and risks
The risks associated with the use of peripheral IV catheter and Foley catheter
with the Reprieve Decongestion Management System are expected to be similar to
other procedure utilizing these catheters. There are also risks associated with
over-hydration and under-hydration along with the risks associated with loop
diuretic therapy for ADHF patients.
*Over-hydration* has a range of potential causes, including insufficient
diuretic dosing, excess saline infusion, and hypotension/low intravascular
volume. *Under-hydration* also has a range of potential causes, including
excess diuretic dosing, insufficient saline infusion, and a rapid increase in
diuresis. The risks of each are identified in more detail below:
Risks of under-hydration:
• Low urine production
• Symptomatic hypovolemia/hypotension
• Electrolytic Imbalance including hyponatremia and hypokalemia
• Abnormal laboratory values
• Dizziness and headaches
• Muscle cramps
• Ototoxicity
• Renal compromise/acute kidney injury
• Arrhythmia
Risk of over-hydration:
• Increased urination
• Symptomatic hypervolemia/hypertension
• Worsening pulmonary function
• Electrolytic imbalance
• Renal compromise
• Arrhythmia
General risks associated with Reprieve DMS:
• Allergic reaction/hypersensitivity to medication, or device materials
• Complications at IV/vascular catheter insertion sites, e.g., bruising,
hematoma, pain, bleeding
• Device malfunction or breakage
• Extravasation/Infiltration at IV/vascular catheter insertion sites
• Infection (IV/vascular catheter insertion site or Foley catheter) or sepsis
• Injury or trauma to the bladder or urethra
• Hemorrhage or bleeding
• Embolism
• Fever
• Hematuria
• Hemodynamic compromise
• Myocardial infarction
• Pain/discomfort
• Pulmonary edema
• Worsening heart failure or low cardiac output
• Anemia
• Death
General risks associated with Study Participation:
• Increased risk of infection or blood loss due to increased blood draws
Complications may occur at any time during the procedure, post-procedure, or
follow-up period. The above risks may require intervention to address the
condition. There may also be other risks that are unforeseen at this time.
Blood tests can hurt or cause bruising. We take 40 ml of blood per visit. In
total, an estimated 440 ml of blood will be taken from you during the entire
study. This amount does not cause problems in adults.
Urine samples are taken for laboratory testing.
Hearing tests are administered by the patient using headphones and an iPad.
Each hearing test takes approximately 2 minutes.
Fortune Blvd 459
Milford, MA 01757
US
Fortune Blvd 459
Milford, MA 01757
US
Listed location countries
Age
Inclusion criteria
1. Hospitalized with a diagnosis of heart failure as defined by the presence of
at least 1 symptom (dyspnea, orthopnea, or edema/swelling) AND 1 sign
(peripheral edema, ascites, jugular venous distension).
2. >=10 lb (4.5 kg) above dry weight either by historical weights or as
estimated by health care provider.
3. Prior use of outpatient oral loop diuretics within 30 days prior to
admission.
4. Patients >= 18 years of age able to provide informed consent (or deferred
consent) and comply with study procedures.
Exclusion criteria
1. Inability to place Foley catheter or IV catheter or other urologic issues
that would predispose the patient to a high rate of urogenital trauma or
infection with catheter placement.
2. Hemodynamic instability as defined by any of the following: systolic blood
pressure <90 mmHg, use of vasopressors, use of IV inotropes to treat
hypotension (systolic blood pressure <90 mm Hg) or suspected/confirmed low
cardiac output/shock, mechanical circulatory support, uncontrolled arrhythmias,
active severe bleeding, or confirmed or suspected cardiogenic shock. Note: In
the absence of the above conditions, use of inotropes to augment diuresis is
permitted.
3. Dyspnea due primarily to non-cardiac causes (e.g., severe chronic
obstructive pulmonary disease or pneumonia).
4. Acute infection with evidence of systemic involvement (e.g., clinically
suspected infection with fever or elevated serum white blood cell count).
5. Estimated glomerular filtration rate (eGFR) < 20 ml/min/1.73m2 calculated
using the MDRD equation or current use of renal replacement therapy (RRT).
6. Significant left ventricular outflow obstruction, uncorrected complex
congenital heart disease, known severe stenotic valvular disease, infiltrative
or constrictive cardiomyopathy, acute myocarditis, type 1 acute myocardial
infarction requiring treatment (within previous week), or any other pathology
that, in the opinion of the investigator, would make aggressive diuresis poorly
tolerated.
7. Inability to follow instructions or comply with follow-up procedures.
8. Other concomitant disease or condition that investigator deems unsuitable
for the study, including drug or alcohol abuse or psychiatric, behavioral or
cognitive disorders, sufficient to interfere with the patient*s ability to
understand and comply with the study instructions or follow-up procedures.
9. Severe electrolyte abnormalities (e.g., serum potassium <3.0 mEq/L,
magnesium <1.3 mEq/L or sodium <125 mEq/l). Note: These are based on
baseline/screening labs. Subjects whose electrolyte levels are repleted cannot
be reassessed for inclusion in the trial.
10. Presence of active COVID-19 infection.
11. Enrollment in another interventional trial during the trial participation.
12. Inability to return for follow-up study visits.
13. Life expectancy less than 3 months.
14. Women who are pregnant. Pregnancy must be ruled out and the patient must
make every effort not to become pregnant.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT05174312 |
| CCMO | NL84955.000.23 |