The SPYRAL AFFIRM study will evaluate the long-term safety, efficacy, and durability of the Symplicity Spyral system in a population of approximately 1300 renal denervation treated subjects with up to 36 months of follow-up, including several sub-…
ID
Source
Brief title
Condition
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The Primary endpoint of office Systolic Blood Pressure (SBP) change at 6 months
will be assessed for all patients in the Main Study Cohort. In addition,
comparison to a pre-specified performance goal for subjects treated in the US
will be performed.
Key objectives related to RDN efficacy, safety, and durability in the full
population and in multiple subgroups will be presented
Secondary outcome
Efficacy objectives will be evaluated for all Main Cohort subjects and for US
subjects in the Main Cohort at each follow up visit based on subject cohort
assignment. Baseline data for subjects in the Continuation Cohort will be
pulled from SPYRAL PIVOTAL-SPYRAL HTN-OFF MED, and SPYRAL HTN-ON MED database
and subjects will be evaluated out to 48 and 60-months post-index procedure as
a secondary cohort only.
• Change in OBP from baseline at 3, 6, 12, 24, 36, 48 and 60-months
post-procedure
• The primary endpoint will be compared to the pre-specified performance goal
subgroups at 6 months for subjects treated in the US.:
• Change in home blood pressure (HBP) from baseline at 3, 6, 12, 24, 36 months
post-procedure (Main Cohort only)
• Change in 24-hour blood pressure from baseline, including day and night
independently, (ABPM Subset & Continuation Cohort) at 3, 6, 12, 24, 36, 48 and
60-months post-procedure
• Change in OBP, HBP and 24-hour blood pressure from baseline will be assessed
in each of the following subgroups as applicable:
• Severe hypertension (baseline office systolic BP >=150 mmHg, despite the
prescription of >=3 antihypertensive medications)
• Age >=65 years
• Chronic kidney disease (eGFR <60 mL/min/1.73m2)
• Atrial fibrillation
• Baseline atherosclerotic cardiovascular disease (ASCVD) risk score ( )
• Coronary artery disease
• Stroke
• Heart rate
• Diabetes mellitus type 2
• Heart failure with preserved ejection fraction
• Subject is unable or unwilling to take antihypertensive medications
• Number of anti-hypertensive medications and classes
• Patients on Beta-blocker therapy at baseline
• Sleep apnea
• Smoking
• Nocturnal hypertension stage I (Nighttime BP of >120/70 mmHg measured by ABPM
or nighttime home BP)
• Morning hypertension stage II (Home BP >145/90 mmHg, between 6:00 AM and
10:00 AM)
• Obese subjects (defined by BMI and/or abdominal obesity)
• Race / Ethnicity, where possible
• Sex at birth
• Percent of subjects achieving blood pressure target reductions and control of
<=140 mmHg as measured by OBP, HBP and ABPM
• Time subject*s blood pressure is controlled through 36-month follow-up or
study exit
• Characterization of anti-hypertensive medication burden over time
• Change from baseline in quality of life as measured by the EQ-5D instrument,
and change in patients* HTN health status measures
• Evaluation of laboratory and clinical characteristics for predictors of
response to renal denervation
• Characterization of procedural characteristics:
• Treatment duration
• Number of ablations per subject
• Number of ablations per kidney
* Branch vs main artery ablations
• Evaluate index procedure costs for subjects participating in the health
economics portion of the study.
• Evaluation of blood pressure as measured by OBP, HBP and ABPM, adjusting for
anti-hypertensive medication burden through 36-months
Background summary
Pls see section 3.1
Study objective
The SPYRAL AFFIRM study will evaluate the long-term safety, efficacy, and
durability of the Symplicity Spyral system in a population of approximately
1300 renal denervation treated subjects with up to 36 months of follow-up,
including several sub-populations. A minimum of 700 subjects will be from the
US. Subsequently, these data will be used to complement data from the SPYRAL
PIVOTAL-SPYRAL HTN-OFF MED trial, SPYRAL HTN-ON MED trial, as well as the
Global SYMPLICITY Registry.
Additionally, in order to gather long-term follow-up data, up to 100 eligible
subjects, initially randomized to the treatment arm in the SPYRAL
PIVOTAL-SPYRAL HTN-OFF MED and SPYRAL HTN-ON MED studies and successfully
treated via the renal denervation procedure, are eligible to be consented for
continued follow up in the SPYRAL AFFIRM study at time of exit from the prior
study. These subjects will attend follow up visits at 48 month and 60 month
post renal denervation procedure they received during the aforementioned
studies.
Study design
The SPYRAL AFFIRM study will consist of two cohorts :
a) Main Cohort: The SPYRAL AFFIRM Main Cohort will consist of all subjects
consented to the AFFIRM study who undergo the renal denervation procedure once
enrolled.
• ABPM Subset: The SPYRAL AFFIRM study will also collect ABPM data for the
first 250 Main Cohort subjects who have a valid ABPM at baseline. (Invalid
ABPMs at baseline are not required to be repeated, those subjects will not be
included in the subset).
b) Continuation Cohort: SPYRAL AFFIRM sites that also participate in the SPYRAL
PIVOTAL-SPYRAL HTN-OFF MED and/or SPYRAL HTN-ON MED studies can enroll subjects
initially randomized to the treatment arm, successfully treated via the renal
denervation procedure for continued follow up through 60 months after the renal
denervation procedure they received in the aforementioned studies. All subjects
that meet the criteria above are eligible to be consented for continued follow
up in the SPYRAL AFFIRM study within one week (+ or -) of exit from the prior
study.
Intervention
Procedure and Follow Up
Upon completion of the required baseline procedures, subjects in the Main
Cohort will undergo renal denervation and be followed for 36-months post
procedure. Once all follow-up visits are completed, the subjects will be exited
from the study.
Subjects consented to the SPYRAL AFFIRM Continuation Cohort will be followed at
48 and 60-month post index procedure from their previous SPYRAL study, for up
to an additional 24 months of study participation from the time of enrollment
to study exit in SPYRAL AFFIRM.
Study burden and risks
Current treatments for uncontrolled hypertension are limited to lifestyle
modifications and pharmacological treatment. Many patients are non-responsive,
non-adherent, or unable to tolerate pharmacological treatment and are left with
few options. The inexorable progression from asymptomatic hypertension to
evidence of end organ disease is well known. Both embolic and thrombotic stroke
as well as both systolic and diastolic heart failure, and progressive renal
dysfunction are known to be companions of chronic hypertension. Beyond
contributing to renal failure, hypertension plagues the treatment of patients
with end stage renal disease treated with dialysis and transplant. In
aggregate, reduction of blood pressure is linearly related to reduction of
mortality and cardiovascular events in population studies , with large
individual patient variability depending on the presence of additional
cardiovascular risk factors, such as lipid abnormalities, diabetes, cigarette
smoking, and antecedent heart disease. Despite the availability of numerous
pharmaceuticals from many different pharmaceutical classes, patients often fail
to attain adequate blood pressure control.
Additionally, pharmaceutical interventions that rely on numerous medications
are plagued with drug interactions and side effects, which contribute to
physician decisions to discontinue medications and patient decisions to not
remain persistent or compliant with the prescribed drug strategies. Non-
adherence to medications is also a well-recognized and common challenge to
blood pressure control. The development of an effective alternative treatment
of hypertension, which offers an adjunct to pharmaceutical care or an
alternative to undesirable pharmaceutical complications, may prove to be of
obvious value to patients, physicians and the health system.
The detrimental effects of uncontrolled hypertension are well established, an
alternative treatment is worth investigation. Renal denervation using the
Symplicity Spyral Renal Denervation system is one such alternative. Although
there are several theoretical risks that could be associated with the device
and procedure, they don*t differ from the commercial setting, in countries
where the device has CE mark.
Also, the likelihood of those risks is believed to be low and will be carefully
monitored in the study.
The potential benefits, including blood pressure reduction and the associated
effects of lowered blood pressure, justify the investigation of renal
denervation in this study.
Endepolsdomein 5
Maastricht 6229 GW
NL
Endepolsdomein 5
Maastricht 6229 GW
NL
Listed location countries
Age
Inclusion criteria
1) Individual is >=18 years of age at time of enrollment (consent)
2) Individual is diagnosed with hypertension and has an average baseline office
systolic blood pressure >=140 mmHg (measured per Appendix B)
3) >=7 days of valid pre-procedure HBP measurements within 30 days prior to the
procedure; consecutive days are preferred but not required (measured per
Section 9.5) Not applicable for the Continuation Cohort
4) Individual agrees to have all study procedures performed and is competent
and willing to provide documented informed consent to participate in this
clinical study. Continuation Cohort must again meet this criterion at time of
SPYRAL AFFIRM Consent
5) Individual was initially randomized to the treatment arm and successfully
underwent the RDN procedure, in either the SPYRAL-PIVOTAL- SPYRAL -HTN-OFF MED
or SPYRAL HTN-ON MED study. Continuation Cohort only
6) Individual has completed their 36- month visit and been exited from the
SPYRAL-PIVOTAL- SPYRAL-HTN OFF MED or SPYRAL HTN-ON MED study. Continuation
Cohort only
7) Individual has a baseline office diastolic blood pressure >=90 mmHg (measured
per Appendix B)
8) Individual has an average systolic baseline home blood pressure >=135 mmHg
(calculated using home blood pressure readings from the first 7 valid days
post-baseline).
Exclusion criteria
1) Individual has renal artery anatomy that is ineligible for treatment
including:
a) At least one main renal artery with a diameter of less than 3 mm or greater
than 8 mm
b) Lacks a main renal arterial vessel that does not allow 4 simultaneous
quadrantic (4SQ) radio frequency ablations in the main renal artery or
equivalent (defined as 4SQ ablations in all branch vessels between 3mm and 8mm)
2) Individual has >50% stenosis in any treatable vessels.
3) Individual has a treatment area within 5mm of a segment in the renal artery
which contains any of the following:
a) Atheroma
b) Calcification, or
c) Renal artery stent
4) Individual has a renal artery stent placed <3 months prior to procedure
5) Individual has undergone prior renal denervation
6) Presence of fibromuscular dysplasia (FMD) (defined as visible beading of the
artery on angiography)
7) Individual has untreated secondary cause of hypertension (either known or
suspected). Secondary cause does not include obstructive sleep apnea
8) Individual has a documented condition that would prohibit or interfere with
ability to obtain an accurate blood pressure measurement using the
protocol-specified blood pressure monitors (e.g., upper arm circumference
outside cuff size ranges or arrhythmia that interferes with monitor*s pulse
sensing or prohibits an accurate measurement) Continuation Cohort must not meet
this criterion again at time of SPYRAL AFFIRM Consent.
9) Individual has a documented confounding medical condition, which in the
opinion of the investigator, may adversely affect the safety of the participant
(e.g., individuals with clinically significant peripheral vascular disease, or
aortic aneurysm)
10) Individual requires chronic oxygen support or mechanical ventilation other
than nocturnal respiratory support for sleep apnea (e.g. CPAP, BiPAP)
11) Individual has an estimated glomerular filtration rate (eGFR) of <45
mL/min/1.73m2, using the 4 variable MDRD calculation (in mL/min per 1.73m2 =
175 x SerumCr -1.154 x Age -0.203 x 1.212 (if subject is of African descent) x
0.742 (if subject is female).
12) Individual has had >= 1 episode(s) of orthostatic hypotension not related to
medication changes within the past year or has a reduction of SBP of >= 20 mmHg
or DBP of >=10 mmHg within 3 minutes of standing coupled with symptoms during
the screening process
13) Individual is pregnant, nursing or planning to become pregnant during the
study. (Note: Pre-menopausal participants must have a negative serum or urine
human chorionic gonadotropin (hCG) pregnancy test prior to angiography)
Continuation Cohort must not meet this criterion again at time of SPYRAL AFFIRM
Consent
14) Individual has polycystic kidney disease, unilateral kidney, atrophic
kidney, or history of renal transplant
15) Individual has a history of narcotic drug abuse or is currently on
Methadone, and would be unlikely or unable, in the opinion of the investigator,
to comply with study follow-up requirements
16) Individual has a history of bleeding diathesis (bleeding disorders such as
thrombocytopenia, hemophilia, significant anemia, or evidence of autonomic
dysfunction where imbalance of sympathetic and parasympathetic tone may alter
disease process in an unpredictable manner) or coagulopathy or will refuse
blood transfusions
17) Individual has documented primary pulmonary hypertension (pulmonary artery
(mPA) >=25 mm Hg at rest, as assessed by right heart catheterization) ( )
18) Individual has severe cardiac valve stenosis for which, in the opinion of
the investigator, a significant reduction of blood pressure is contradicted.
19). Individual has documented type 1 diabetes mellitus or poorly-controlled
type 2 diabetes mellitus with glycosylated hemoglobin greater than 8.0%. (If
the glycosylated hemoglobin in the subjects *s records is >3 months old (from
the date of baseline visit), or history of uncontrolled blood sugars raises
concern it is required to analyze glycosylated hemoglobin as part of baseline
labs).
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 | NCT05198674 |
| CCMO | NL81433.096.22 |