The objective of this study is to assess the safety and feasibility of the Doraya Catheter in the treatment of subjects hospitalized with congestive AHF, with insufficient response to diuretic therapy.
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Primary Safety: Device or procedure related Serious Adverse Event (SAE) rate
through 30 days post index procedure as adjudicated by a Clinical Events
Committee (CEC).
- Primary Feasibility: Technical success, defined as ability to position the
device below the renal veins, to regulate the flow in the IVC using the device
by creating a gradient pressure of at least 2 mmHg, and to withdraw the device.
Secondary outcome
Secondary Observational Measures:
Clinical and observational measures (baseline, during treatment, 24 hours
following treatment and at discharge):
* Congestion signs & symptoms: Dyspnea (Likert scale), orthopnoea, pulmonary
rales, jugular venous distension and peripheral edema.
* Renal function: Urea, creatinine, eGFR, hourly urine output, daily fluid
balance,
daily diuretic dose.
* Circulatory system hemodynamics (during treatment only): Renal Venous
Pressure (RVP, continuously measured through the catheter), Right Atrial
Pressure (RAP) or Central Venous Pressure (CVP), peripheral venous pressure
(PVP), Heart rate
* Using a Swan-Ganz catheter: Cardiac Output, Pulmonary Artery Pressure (PAP),
mixed venous (pulmonary artery) saturation and Pulmonary Wedge Pressure (PWP)
* Clinical measures: Body weight, serum electrolytes, sodium, potassium,
BNP/NT-proBNP, blood pressure, length of hospital stay.
* Medical HF therapy including need for intensification of therapy (e.g.,
mechanical ventilation/therapy, circulatory support with inotropes, use of
vasodilators). Clinical and observational measures 7 days, 30 & 60 days after
treatment:
* Clinical manifestations of worsening or persistent heart failure as defined
by at least one of the following: new, persistent or worsening dyspnea,
orthopnea, pulmonary basilar rales/crackles, jugular venous distension.
* Re-hospitalization
Background summary
Acute heart failure (AHF) is often a life-threatening event requiring urgent
medical attention and can mark a transition to a more debilitating phase of the
disease. About 1/6 (1M out of 6M in the US) of the HF patients are hospitalized
due to AHF each year. Up to 10% of patients with AHF die in hospital and 20*40%
die within a year, while 20*25% are readmitted to the hospital within 30 days.
2.1 Importance of Congestion in AHF: diagnosing and therapy guidance
Available data suggest that the main reason for hospitalization for worsening
HF is related to the symptoms (dyspnea or breathlessness; leg swelling) of
congestion, manifested also by signs [e.g. jugular venous distension (JVD),
rales, and edema] of congestion, rather than low cardiac output4. Although
congestion is the main reason for hospitalization, many patients are discharged
without losing body weight and with persistent signs of congestion. Congestion
is associated with a poor prognosis and is an important target for therapy.
2.2 Management of AHF patients (ESC 2016 Guidelines4)
Diuretics are a cornerstone in the treatment of patients with AHF and signs of
fluid overload and congestion. Diuretics increase renal salt and water
excretion and additionally have some vasodilatory effect.
The initial approach to congestion management involves I.V. diuretics with the
addition of vasodilators for dyspnea relief if blood pressure allows. To
enhance diuresis or overcome diuretic resistance, options include dual nephron
blockade by loop diuretics (i.e. furosemide or torasemide) with thiazide
diuretics or natriuretic doses of MRAs. However, this combination requires
careful monitoring to avoid mal effective alterations in potassium levels
(hypokaliemia or hyperkaliemia, derived by the type of diuretic agents used)
and moreover renal dysfunction and hypovolaemia.
Intravenous vasodilators are the second most often used agents in "Warm" AHF
for symptomatic relief; however, there is no robust evidence confirming their
beneficial effects. Vasodilators seem to have a negative effect on AHF patients
with worsening renal function, manifested in escalation of WRF correlated to
the addition of vasodilators to intravenous diuretics compared with intravenous
diuretics alone.Thromboembolism prophylaxis with heparin or another
anticoagulant is recommended unless contraindicated or unnecessary (because of
existing treatment with oral anticoagulants). Use of an inotrope should be
reserved for hypotensive AHF patients with a severe reduction in cardiac output
resulting in compromised vital organ perfusion, which occurs most often in
hypotensive AHF.
2.3 Diuretic Resistance in AHF patients
The mainstay of AHF treatment relies on effective diuretic regime, which
mandates functional kidneys (as the target organ for those agents). Inevitably,
deterioration in kidney function (manifested by reduced kidney filtration or
Glomerular Filtration Rate - GFR), results in diminished efficacy to
physiologically regulate fluid status (by altering fluid retention or
urination), namely Diuretic resistance.
Diuretic resistance was well proven to independently have clinical importance,
manifested in increased mortality and higher re-admission rates10. To date
there is no formal guideline to monitor diuretic response4 and the diuretic
resistant population still lacks better definition and treatment options.
2.4 Current Management of Diuretic Resistant AHF Patient
The development of Worsening Renal Failure (WRF) in patients with congestion
related to AHF is a common but difficult clinical problem to manage as the
kidney plays a major role in controlling volume status. The incentive is clear,
as the association between impaired or worsening renal function and mortality
in patients with AHF strongly suggests the possibility that an effective
treatment should improve those patients' outcomes.
Nevertheless, to date there is no single effective approach to the management
of this condition, above all, to those patients which have diuretic resistance.
Current approach for poor responders to initial dose of diuretics is to
increase dosage and / or to add different type of diuretic until adequate
diuresis occurs. Low cardiac output is usually not the main cause for
hospitalization and the patients usually present with normal to high blood
pressure. The *wet & warm* group targeted by this device is highly associated
with persistent volume overload, and many HF patients are discharged with
persistent signs and symptoms of congestion and/or a high LV filling pressures
as previously mentioned11. Hospital stay for these
patients widely varies across the globe: in the US, average length of stay is 6
days (4-10 days for vast majority of patients), with 24% of readmission in 30
days. In Europe, average length of stay is much longer, 7-14 days, with
markedly reduced readmission rates to high single
digit.
Study objective
The objective of this study is to assess the safety and feasibility of the
Doraya Catheter in the treatment of subjects hospitalized with congestive AHF,
with insufficient response to diuretic therapy.
Study design
This study is a prospective, single-arm, open label, multi-center
first-in-human study designed to evaluate the safety and feasibility of the
Doraya Catheter in the treatment of congestive AHF, with insufficient response
to standard diuretic therapy.
Intervention
The Doraya is a percutaneously delivered catheter which is deployed
over-the-wire using fluoroscopy and positioned in the inferior vena cava, below
both renal veins (deployment is similar to IVC filter procedure technique).
Once its position is validated using radiopaque markers, the operator deploys
the catheter by pulling back the catheter outer shaft. The catheter*s
self-expandable nitinol frame will then be opened in the vessel, allowing the
operator to control and regulate the flow in the IVC. The guidewire will then
be removed to allow monitoring of local hemodynamic pressures (renal and
peripheral venous pressures).
The catheter self-expanding Nitinol frame is attached on the distal end of the
catheter, and is covered by a polyurethane layer at its the distal end.
Manipulation of the distal end of the frame (aperture like configuration)
manages the flow, which is monitored by pressure measured through the
catheter. While the catheter is deployed in the IVC (up to 24 hours), the
operator can use the catheter handle to control the flow in the vessel by
constricting or opening the catheter. The distal element of the catheter is
partially coated with polyurethane which is coated with passive
hydrophilic material (HydromedTM, Advansource Biomaterials) to prevent cellular
adhesion and thrombus formation.
Removal is done under fluoroscopy guidance by insertion of the guidewire,
re-mounting the outer shaft on the catheter frame, and removing it from the
body. Further information can be found in the Instructions For Use (IFU).
Detailed training on device handling, IFU and IB, covering instructions on
catheter insertion, operation and withdrawal, will be provided by the Sponsor
to each performing physician during a Site Initiation Visit.
Study burden and risks
Tekst directed to the patient:
You may experience side effects while being in the study. Because this is the
first time that the Doraya catheter is used in humans, in addition to the risks
described below, there may also be risks or side effects that are unknown at
this time. Everyone taking part in the study will be watched carefully for any
side effects. Side effects may be mild or very serious. Your health care team
may give you medicines to help lessen side effects. Some side effects may go
away after treatment with the Doraya is stopped. In some cases, side effects
can be serious, long lasting or may never go away. There also is a risk of
death.
In this study you are required to undergo two (2) catheterization procedures,
which in rare cases can cause pain or discomfort during catheter insertion, and
later because of prolonged laying down. There is a possibility, while injecting
contrast solution that you feel discomfort around your ribcage, or feel a sense
of heat. However, these sensations usually pass after a few seconds.
The risks that may be associated with the Doraya treatment are listed below,
divided to potential risks during catheter insertion, during the temporary
procedure and following the removal of the catheter.
Risks during insertion of the Doraya catheter include:
* Misplacement of the device may occur during insertion. Highly unlikely, but
will require the investigator to re-position the device during catheterization.
* Leakage of contrast media from the normal intravascular compartment into
surrounding soft tissue - is highly unlikely and may prolong the initiation of
the procedure.
* Injury to the Inferior Vena Cava: Minor injury is expected in most cases,
similar to other vascular interventions. Perforation or penetration are of very
low likelihood, but will require a medical attention.
* Air embolization is a small air bubble that may reach the lungs during the
catheter insertion, similar to other venous interventions. Low likelihood with
a minor clinical risk.
Risks during procedure:
* Risks to the heart include:
- Arrhythmia (changes in heartbeat)
- Significant drop in blood pressure may happen due to full occlusion of the
blood flow. While unlikely, they will require immediate medical attention.
* Risks to the lungs include:
- Thrombosis or embolization, the formation of blood clots in the veins or on
the device, may occur during procedure and may reach the lungs. As the
procedure includes various anti thrombotic treatment it is unlikely, but will
require medical attention to prevent long term effect.
* Risks to the insertion site include:
- Infection and thrombosis (formation of blood clot at the site) are highly
unlikely, and will require an immediate medical attention.
- Hematoma, collection of blood outside the blood vessels, is a common
complication of catheters. While of low clinical risk, it will require medical
attention.
- Low local pain is associated with catheters. While of low clinical risk, it
will require medical attention.
* Systemic risks include:
- Leg Ischemia (poor blood supply) and/or leg swelling may occur during the
procedure due to limiting blood back flow to the heart, and are associated with
pain. These conditions, while of low clinical risk, will require medical
attention.
- Thrombocytopenia is a condition characterized by abnormally low levels of
thrombocytes, also known as platelets, in the blood. Highly unlikely to occur,
and will require medical attention
- Excessive procedural and post procedural bleeding are highly unlikely to
occur, and will require immediate medical attention
- Worsening of Heart Failure symptoms
- Death
Other currently unknown risks and discomforts could appear. It is therefore
very important that any new health problem is quickly reported to the
investigator, regardless of whether or not you think it has to do with the
study.
Throughout the course of the treatment, your doctor will watch your progress
closely, and will adjust your medicines as needed. If your doctor decides that
the Doraya catheter is unsuccessful at any point in time, he will stop the
treatment and offer you other choices for your treatment and care. Your doctor
will discuss this with you.
Giborei Israel St. 7
Netania 4250407
IL
Giborei Israel St. 7
Netania 4250407
IL
Listed location countries
Age
Inclusion criteria
1) Subject is >18 and <85 years of age.
2) Subject is hospitalized with primary diagnosis of congestive AHF.
3) Evidence of fluid overload as indicated by 2 or more of the following criteria:
a) peripheral edema *2+
b) jugular venous distension *7 cm H2O
c) radiographic pulmonary edema or pleural effusion
d) enlarged liver or ascites
e) pulmonary rales or paroxysmal nocturnal dyspnea, or orthopnea.
4) Subject insufficiently responds to standard diuretic therapy, meeting the following criteria:
Sufficient diuretic treatment:
a) >80 mg furosemide per day or an equivalent, or;
b) >1.5X of the subject chronic baseline diuretic level
With at least of one of the following:
a) reduction of <1 Kg/day in subject weight, or;
b) <1ml/kg/hour Urine output (for a duration of at least 4 hours), or;
c) IVC with no inspiratory collapse by cardiac ultrasonography
5) Brain natriuretic peptide (BNP) *400 pg/mL or N-terminal-pro-brain natriuretic peptide (NT-proBNP) *1,600 pg/ mL.
6) Subject understands the nature of the procedure and provides written informed consent prior to any study specific assessments.
7) Subject is willing and able to comply with the specified study requirements and follow-up assessments, and can be contacted by telephone.
8) Evidence of cardiac etiology as per cardiac ultrasonography.
9) IVC with no inspiratory collapse by cardiac ultrasonography.
10) Urine output <1ml/kg/hour, for minimum duration of 4 hours, preferably measured through a urinary catheter.
11) CVP>12 mmHg confirmed at the beginning or prior to the catheterization procedure.
Exclusion criteria
1) Systolic blood pressure <90 mmHg at the time of screening.
2) Acute myocardial infarction or acute coronary syndrome within past 7 days.
3) Known LVEF < 10% by echocardiography within 1 year prior to enrolment.
4) Complex congenital heart disease (e.g. Tetralogy of Fallot subjects, single ventricle physiology).
5) Known active myocarditis, hypertrophic obstructive cardiomyopathy, constrictive pericarditis or cardiac tamponade.
6) Severe Aortic valvular disorder (i.e., hemodynamically relevant valvular diseases such as severe stenosis\severe regurgitation) or Severe mitral disease with planned intervention.
7) Severe renal dysfunction (eGFR <18 ml/min/1.73 m2 BSA) or subject is on chronic dialysis.
8) Subject has history of deep vein thrombosis and/or pulmonary embolism
9) Evidence of cardiogenic shock with organ hypo-perfusion.
Current or need of mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device),
10) Subject with bleeding disorder which limit the use of antiplatelet and/or anticoagulant therapy (e.g. Thrombocytopenia with platelets count <100,000, anemia with hemoglobin <9 mg/dL)
11) Subjects with a known infra-renal IVC diameter of <14mm
12) Open or infected wounds in the legs.
13) Subject is pregnant or lactating. Pregnancy confirmed by positive urine or serum test.
14) Subject with advanced liver disease or serum Albumin<2.5 g/dL
15) Evidence of active systemic infection (documented by either one of the following: fever >38°C, ongoing uncontrolled known infection (i.e. inflammatory parameters not decreasing despite * 48 hrs of antibiotic treatment)
16) Severe obesity (BMI >35).
17) Subject with known hypersensitivity to Nickel.
18) Subject with history of radiation therapy to lower abdomen.
19) Contraindication to recommended study medications or intravascular contrast material that cannot be adequately controlled with pre-medication.
20) Moribund subject or subject with severe or deteriorating damage in more than 3 critical body systems or requiring inotropic therapy for survival.
21) Concomitant disease expected to cause death in * 90 days
22) Any other medical, social, or psychological issues that in the opinion of the investigator preclude the subject from receiving this treatment, or the procedures and evaluations pre- and post-.
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 |
|---|---|
| CCMO | NL63504.100.17 |