The primary objective of the study is to evaluate the safety and tolerability of the Occlutech® AFR device by assessing the incidence of SADEs in the 3 months following implantation. Secondary objectives are related to safety and efficacy:• To…
ID
Source
Brief title
Condition
- Pulmonary vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary safety endpoint of the study will be assessed after 3 months
following implantation and is defined as the rate of serious adverse device
effects (SADE).
Secondary outcome
Secondary study parameters/outcome of the study (if applicable) (in English):
The following secondary safety variables will be collected within the period of
12 months after implantation and used to assess the safety of the Occlutech®
AFR device:
• Rate of all SAEs;
• Rate of all (S)ADEs
The following secondary efficacy variables will be assessed by comparison of
the values with baseline data and expressed as absolute and percentage changes:
Mechanical Performance
Assessments by color-doppler echocardiography and angiography/fluoroscopy:
• Device placed in situ [as assessed by the Investigator];
• Evidence of RIGHT TO LEFT shunt through the AFR device [as assessed by the
Investigator];
Clinical Performance;
• NYHA status [Classification by investigator];
• Transcutaneous oxygen saturation [%];
• Rate of syncopal events;
• Dosage of diuretics;
• Dosage of PH-related medication.
Functional Variables (ECHO, 6MWT, CPX)
• Ratio of right ventricle size to left ventricle size [mm/mm];
• Size of left ventricle in diastole (cm2);
• 6-Minutes-Walk Test [m];
• VO2max [ml O2/min];
• Transcutaneous saturation at max.
Laboratory Variables
• NT-Pro-BNP [pg/ml];
• Creatinine [µmol/l];
• CholinEsterase [kU/l].
Hemodynamic Variables
• Right atrial pressure (mmHg);
• Right atrial pressure -to Left atrial pressure gradient;
• Cardiac index [(l/min)/m²]
Background summary
Patients with severe pulmonary hypertension (PH) develop a reduction and decay
of the pulmonary vasculature. The right side of the heart should pump the full
cardiac output through this narrowed vascular system, which also has high blood
pressure and increased pulmonary vascular resistance. In a compensated state,
the heart can increase the workload. However, in the course of time the heart
can decompensate. This leads to increased pressure in the right atrium. Because
the size of the right half of the heart increases, tricuspid dysfunction and
eventually heart failure develop in many cases, combined with reduced cardiac
output and reduced filling and output of the left side of the heart. Most
patients die due to a combination of right heart failure, with low cardiac
output from the left.
Patients with PH suffer from reduced exercise capacity and may eventually
develop signs of reduced cardiac output and low blood pressure due to right
heart failure. Periods of acute increase in pulmonary vascular pressure with
acute decrease in cardiac output may lead to fainting. Eventually, these
patients die of blocked or significantly reduced blood flow through the
pulmonary vascular system and / or arrhythmias due to insufficient coronary
perfusion.
By means of an atrial flow regulator (AFR) an artificial connection is
established via the interstitutional septum through which blood flows when the
volume of blood on the right side is too high. This would reduce the pressure
in the right heart side and reduce the clinically important right heart
congestion. Furthermore, the left side of the heart gets extra blood volume,
which increases stroke volume, cardiac output, blood pressure and organ
perfusion. Probably acute fainting and acute right heart decompensation and
mortality occurs less.
The usual treatment for patients with severe pulmonary hypertension, which has
since been very well described in internationally accepted and published
guidelines, is treatment with a variety of medications, including
anticoagulants, diuretics, digitalis preparations, oxygen, vasodilators,
calcium antagonists, prostacyclines and prostacyclin- analogs, endothelin
receptor antagonists and phosphodiesterase inhibitors. Nonetheless, these
seriously ill patients usually have a poor prognosis resulting in right heart
failure and death. If patients reach NYHA stage III or higher, lung
transplantation is the only option for these patients. Currently, patients are
often offered balloon atrial septostomy (BAS).
The advantage of BAS is the increase in cardiac output as a result of the extra
blood volume by making a passage between the right and left atrium. This
relieves the right ventricle and the entire venous system, with reduction of
clinical symptoms. The overall survival of patients who have undergone such
treatment is increasing. That is why this procedure is used to 'bridge' the
time until actual lung transplantation takes place.
The disadvantage of a BAS is that the artificial passage may be too large,
causing dangerous desaturation and potential death. The passage can also be
closed by heart cells in the short term, requiring a new intervention, with
additional risk burden for the patient.
The AFR is intended to realize both a correct diameter of the artificial
passage and to prevent its growth. Atrial flow regulators are considered
suitable for treatment of a certain group of patients with pulmonary
hypertension according to the most recent international guidelines of the
American Heart Association.
Study objective
The primary objective of the study is to evaluate the safety and tolerability
of the Occlutech® AFR device by assessing the incidence of SADEs in the 3
months following implantation.
Secondary objectives are related to safety and efficacy:
• To evaluate the safety and tolerability of the Occlutech® AFR device by
assessing the incidence of SADEs between 3-12 months following implantation.
• To evaluate the improvement in Right-Heart-Failure in the 3 months, in the 6
months and in the 12 months following implantation;
• To evaluate the improvement in number of syncopal events due to pulmonary
hypertension in the 3 months, the 6 months and the 12 months following
implantation.
Study design
This is a prospective, non-randomized, pilot study to assess safety and
efficacy of a novel Atrial Flow Regulator (AFR) in patients with pulmonary
hypertension in a phase-2 design.
Patients will be screened within the week before the implantation of the AFR.
Eligible patients who signed the informed consent form will undergo Balloon
Atrial Septostomy followed by implantation of the AFR device under standard
clinical procedures. Follow up period after implantation will consist of 6
visits in a period of 360 days.
Intervention
Patients will undergo Balloon Atrial Septostomy followed by implantation of the
AFR device under standard clinical procedures.
At day of implantation, there will be a catheterization, providing the
definition of the PH and for the AFR implantation procedure. Catheterization
will be repeated after 3 months to evaluate changed hemodynamics, including
fluoroscopy to judge position of the device. This 3 months FU is in common
practice in the EU and USA and is, together with the radiation burden within
the currently accepted mode of care.
Catheterization will be conducted according to a study specific catheterization
protocol.
During the course of the study, blood is collected for laboratory analysis,
ECGs and transthoracic echocardiography are made and 6-miutes walking test and
Cardiorespiratory Test with lung function are conducted.
Study burden and risks
Patients with PH are often offered BAS. The advantage of the BAS is the gain in
cardiac output due to the additional blood volume provided by the right-to-left
shunt through the BAS. This, on the other side of the heart, offloads the right
ventricle and the entire venous system, with reduction of the clinical
symptoms. Survival of such treated patients is increased, thus, this procedure
is used to *bridge* the time until actual lung transplantation is happening.
Potential risks related to the intended use and foreseeable misuse of the
Occlutech® AFR are identified and mitigated on an ongoing basis. Anticipated
potential risks of the Occlutech® AFR device are associated with:
• Device contamination
• Vessel or unintended and excessive cardiac perforation
• Use of oversize or undersize device
• Complications of transseptal puncture
• Wrong size dilatation balloon selection
• Wrong usage of delivery system
• Device design is not suitable for the septal puncture morphology
• Use of wrong/incompatible sheath (system)
• Use of incompatible pusher: Pusher size is larger or smaller than it is
supposed to be
• Incorrect positioning of device
Risk control measures were undertaken to reduce the probability of unacceptable
and borderline acceptable risks. Where ever possible, priority was given to
mitigating the risk first through design changes to eliminate it and if this
was not feasible, by integrating protective measures in the medical device
itself or in the manufacturing process to minimize the risk. Risks due to human
factors that could not be eliminated or checked in advance, such as mistakes in
the implant or explant procedures will be mitigated by including clear warnings
and cautions in the literature and packaging accompanying the device and by
limiting implantation use to experienced and trained interventional
cardiologists.
As described in section 5.3, a full risk analysis was performed during the
development of the Occlutech® AFR device to anticipate and eliminate or at
least minimize all foreseeable
Occlutech® AFR device related risks. However - as with any new device - it is
possible that unknown risks remain that will only become apparent as more
experience is gained with the device. The safety of the study patients is of
paramount importance and will be monitored throughout the study at all times.
It is possible that the study will show the Occlutech® AFR device is not
suitable for its intended use. In this event, future patients will be spared
exposure to the Occlutech® AFR device and information may have been gained to
develop alternatives. Patients in this study may still have benefitted from
their participation in the form of a closer follow-up and a positive altruistic
feeling.
Patients will be requested to attend visits on a regular basis. It is possible
that this will be uncomfortable or inconvenient for them. Patients will be
reminded that the information they provide is confidential, that it will be
used to better the care they and fellow patients receive, and that their
continued participation is voluntary.
The disadvantage of an atrial septostomy is
• artificial shunt may be too large
• may occlude within the short term
• may result in repeat BAS
• anticoagulation with Warfarin and analogues is recommended life-long
Advantage of the AFR device is:
• securing the BAS to remain open
• preventing BAS oversizing and systemic desaturation
• plasmatic anticoagulation is not necessary, platelet inhibition should occur
for 6 months
• the ability to plan the size of the intended right-to-left shunt creates
further safety in this specific intervention and in the care of the patient in
general
• the expected absence of above complication in these severely ill and unstable
patient will likely result in less morbitiy and mortality.
In conclusion, the benefits of AFR devices outweigh by far the procedural and
device related risks.
La Cours gata 2
Helsingborg 25231
SE
La Cours gata 2
Helsingborg 25231
SE
Listed location countries
Age
Inclusion criteria
Each patient must fulfill ALL of the following criteria and details:1. Age is >=
18 / >= 6 years (Phase 1 / Phase 2).
2. Patient consents to participation
3. The patient or his/her legal representative should have the ability to
fluently speak and understand
the language in which the study is being conducted. If the patient speaks a
different language,
then a sentence-to-sentence translation for unequivocal understanding must be
provided.
4. Written, informed consent by the patient or her/his legally-authorized
representative for participation in the study.
5. Patient agrees to comply with the follow-up schedule.
6. Patient has had a successful BAS procedure and is in a stable hemodynamic
state, as assessed by the Investigator
7. Conventional treatment options for the patient are exhausted according to
European Society of Cardiology and American Heart Association guidelines
8. SpO2 >= 86 % (pulsoxymetric measurement)Further, the patient must fulfill ALL
criteria and details of
EITHER *Syncope* (Group-A-PH) OR *RV-Failure* (Group B-PH).9. *Syncope* (Group-
A-PH)
9.1. Syncope due to acute PH episodes (as defined by exclusion of other causes)
9.2. Other causes of syncope must have been actively excluded
9.3. Syncope (Black-out) or pre-syncope (episodic dizziness) >2 last 3 months
9.4. PH (defined as mean pulmonary artery pressure > 25 mmHg, or pulmonary
vascular resistance
of > 3 Wood Units) must exist, RV-failure is however not a prerequisite.10. *RV-
Failure* (Group B-PH)
10.1. Right heart failure, chronic and clinically severe
10.1.1. NYHA class III or worse
10.1.2. 6 min walk < 320 m
10.1.3. Signs of venous congestion (distended veins, edema, ascites, etc)
10.1.4. Symptomatic disease resulting in 1 or more PH-related hospitalization
over the last 12
months. Elective hospital admissions solely for the purpose of performing
diagnostic procedures
do not count for this.10.2. Severe pulmonary hypertension as evident by
echocardiography
Echocardiographic:
10.2.1. RV larger than LV;
10.2.2. RA larger than LA;
10.2.3. Atrial septum bulging into left atrium
10.2.4. Ventricular septum bulging into the left ventricle
10.2.5. Reduced (below age-related normal mean value) TAPSE10.3. Severe
pulmonary hypertension as evident by CATH
CATH-data:
10.3.1. Mean RA pressure (RAP) >= 10 mmHg and <= 20 mmHg;
10.3.2. Mean LA pressure (LAP) <= 15 mmHg
10.3.3. Mean RAP > mean LAP;
10.3.4. Mean pulmonary arterial pressure >25 mm Hg
10.3.5. Echocardiographically demonstrated continuous right to left shunt
following balloon
atrial septostomy (BAS) and before AFR device implantation
sible risks of c
Exclusion criteria
A patient must be denied access to the study if one or more of all the
following criteria are present as evaluated by medical history, laboratory test
or other, as appropriate:Processes which interfere medically with invasive
device implantation
1. Local or generalized sepsis or other acute infection(s)
2. Thrombophilic coagulation disorder
3. Allergy to nickel and/or titanium and/or nickel/titanium-based materials
4. Allergy to anti-platelet, -coagulant, or -thrombotic therapy
5. Intolerance to contrast agents
6. Participation in other medical trials shorter than 30 days before the
intended AFR implantation
procedure
7. Pregnancy - (assessed in patients with child bearing potential by urine dip
stick)
8. Any intracardiac intervention within the last 30 days
9. Thickness of atrial septum > 12mmORProcesses which would technically disturb
the safe intervention as planned
1. Occluded inferior vena cava access
2. Previous ASD/PFO closure device in place
3. Intracardiac thrombusORany other circumstance that, in the opinion of the
Investigator, might interfere with the implantation, might affect the patient*s
well-being thereafter or might interfere with the conduct and follow-up within
the study in general.
itiy and morta
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 | NCT03022851 |
| CCMO | NL67794.042.19 |