Download The US ROX HTN Trial Design

US ROX HTN Clinical Trial Design:
Reason and Rational
Krishna Rocha-Singh, MD
Chief Scientific Officer
Prairie Heart Institute Saint John’s Hospital
Springfield, IL
Krishna Rocha-Singh, MD
Within the past 12 months, I or my spouse/partner have had a
financial interest/arrangement or affiliation with the
organization(s) listed below.
Affiliation/Financial Relationship
Company
• Grant/Research Support
• Consulting Fees/Honoraria
• Medtronic
• Medtronic, Alucent, Zimmer-BioMet,
ROX Medical
• Major Stock
Shareholder/Equity
• Royalty Income
• Ownership/Founder
• Intellectual Property Rights
• Other Financial Benefit
• PQ Bypass
•
•
•
•
None
Convergence Consulting, LLC
Yes
VIVA Board Member
The Pathophysiology of
Structural Hypertension
Feed-forward loop involving blood pressure parameters, circulatory damage and arterial stiffness
Kapil et al. Curr Hypertens Rep 2015
Age Related loss of Aortic Elasticity
Underlies HTN Treatment Failure
% Uncontrolled
85% of uncontrolled
patients are over 50 yr
Isolated
Systolic
Htn
ISH
aka,
‘Structural
Hypertension’
Sys/Dias
Htn
Isolated
Diastolic
Htn
Franklin et al, Hypertension 2001
ROX Coupler Device
Arteriovenous ROX Coupler and deployment catheter
Reproduced by permission of ROX Medical, San Clemente, CA, USA.
ROX Coupler
• Using a venous segment to reduce effective
arterial volume :
– Restores aortic elasticity at lower filling volumes
in aged vessels
– Reduces mean and peak BP
– Reduces BP variability and volume sensitivity
• Reducing pulse wave propagation velocity
eliminates systolic pressure stacking
Fixed 4mm Diameter Arteriovenous Anastomosis
~ 800 cc shunt
Increase Arterial Compliance, Decrease Vascular Resistance
Placement between
Iliac Artery & Vein
Immediate, Verifiable Response
No Sham, Placebo,
Hawthorne Effect
CLOSED
182 mmHg
OPEN
158 mmHg
CLOSED
180 mmHg
The ROX Coupler is NOT commercially available in the United States. CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.
The ROX Coupler is CE marked for Hypertension and is commercially available in the European Union.
Immediate, Significant BP Reduction Upon
Placement of the ROX Coupler
The immediate BP reduction eliminates
the possibility of placebo, sham
or Hawthorne effect
An ‘On-the-Table’, Significant BP Reduction in
All Patients (average BP decline: -28/-15mmHg)
Systolic BP
186-180 mmHG
150-153 mmHG
~60
~72
( mmHg )
Diastolic BP
ROX CONTROL HTN Study: Six-Month Results
Change from baseline in blood pressure at 6 months
Data are mean (SD). SBP=systolic blood pressure. DBP=diastolic blood pressure. OBP=office
blood pressure. ABP=ambulatory blood pressure. AV=arteriovenous.
Lobo et al. Lancet 2015
ROX CONTROL HTN Study: Six-Month Results
Includes left
and right side
implants
Only right
side US trial
Adverse events related to AV coupler placement or device
Lobo et al. Lancet 2015
Venous Stenosis:
An Easily Managed Complication




Venous stenosis, a fibrotic “hour-glass” narrowing
of the vein occurs cranial to the anastomosis
Late onset edema is the typical sign, 6-9 months
post procedure
PTA with venous stenting resolved stenoses
~100% success rate with no reoccurrences
Venous Stenosis Occurrence - RH-02 HTN Randomized Trial
Patients with VS
50
100%
n=42
40
# Patients
80%
Cumulative Incidence
30
100% Resolution
20
6
10
5
1
60%
40%
20%
1
0
0%
0
3
6
9
12
15
18
Months post Coupler Placement to Onset
 Approved FDA IDE to initiate a pivotal RCT for
HTN control
 Trial enrollment expected to begin early Q2
2017
The US ROX HTN Trial Design:
Impact on AV Fistula Physiology on Trial Design?
• 1:1 randomized sham controlled, doubleblinded (patient and HTN physician) trial
• Primary Endpoint: Change in mean 24 h ABPM
at 6 months
--Secondary Endpoint: Change in mean OBP at
6 months
• Safety Endpoint: Procedural and AEs through
12 months
BP Medications Run-In Screening
A Sustainable Dosing Regimen
• Stable regimen of at least 3 months consisting
of a diuretic AND
--Two additional anti-hypertensives of
difference classes; guideline- or labeldirected dosing; OR
--Documented intolerance to at least three
of 4 major classes of anti-hypertensives
(ACE, ARB, B-blocker, CCB)
Maintain drug regimen for at least 6 months
post-randomization
The US ROX HTN Trial Design:
Key Inclusion Criteria
• Key Inclusion Criteria:
--OBP ≥155 mmHg at all screening visits AND
≥160 at one visit; OR OBP ≥150 mmHg AND
one ER visit or hospitalization in the past 12
months for antihypertensive crisis
• 24 hour ABPM ≥140 mmHg
• Site expertise in HTN diagnosis and treatment
The US ROX HTN Trial Design:
Key Exclusion Criteria
•
•
•
•
eGRF <45 mL/min/1.73m2
Significant venous disease and/or PAD
Moderate/severe valvular disease
LVEF ≤45%, mean PAP >25mmHg, PCWP >15
mmHg at time of right heart cath
• History of DVT/PE
Minimizing the Hawthorne Effect
• Patients will attend 3 screening visits:
--Measure OBP at each screening visit
--Home medication compliance logs to
reinforce consistence, stable dosing
• ECG, TTE, venous DUS and ABIs will also
be performed
Post-Randomization Follow-up
• 1, 3, 6, 12 month clinical follow-up performed
by a blinded investigator/designee
• Goal to maintain pre-randomization medical
regimen through 6-months
• Safety considerations will allow for medication
adjustments (hypotension/hypertension, etc.)
US ROX HTN Trial
• The first therapy which is effective for HTN
consequent to loss of aortic elasticity- “Adult
Hypertension”
• The ROX randomized, double-blinded, sham
controlled trial in hypertensive patients on a
‘stable and consistent’ antihypertensive
regimen, maintained through 6-months will
assess the safety and efficacy of this novel
concept
THE END