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Instructions:You will prepare a PPT presentation for the journal club on Randomized trials of intensive versus standard blood pressure control (SPRENT trial)Ensure to follow the ASHP format (background and overview, methods, results, discussion, and conclusions). The format is attached.In addition, JC presentations examples are uploaded for your reference. if there is any question i will chick just send me
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Endovascular Ultrasound Renal
Denervation to Treat
Hypertension (RADIANCE II)
Monaz Engineer, PharmD
PGY-2 Cardiology Pharmacy Resident
University of Chicago Medicine
July 28th, 2023
1
Introduction
• In the past decade, endovascular
catheter-based renal denervation
(RDN) has emerged as a potential
adjunctive option for resistant
hypertension (HTN)
• RDN utilizes radiofrequency to ablate
the afferent and efferent sympathetic
nerves in the outer-most wall of the
renal arteries
Denker MG, et al.Cardiovasc J. 2015 Oct-Dec;11(4):240-4.
2
Introduction
Activation of renal efferent nerves
↑ noradrenaline production
↑ renal vasoconstriction
↑ renin release
↑ increased salt and water retention
Activation of renal afferent nerves
↑increased central sympathetic
outflow to various organs
Denker MG, et al.Cardiovasc J. 2015 Oct-Dec;11(4):240-4.
3
Introduction
Activation of renal efferent nerves
↑ noradrenaline production
↑ renal vasoconstriction
↑ renin release
↑ increased salt and water retention
Activation of renal afferent nerves
↑increased central sympathetic
outflow to various organs
Denker MG, et al.Cardiovasc J. 2015 Oct-Dec;11(4):240-4.
4
Background
• Early trials (SYMPLICITY HTN-3 2014 and DENERHTN 2015) of RDN
reported inconsistent results
• No significant reductions of systolic blood pressure (SBP) in patients
with resistant hypertension ~6 months after renal-artery denervation
as compared to sham-control or standard medication therapy
• Four subsequent sham-controlled trials provided evidence in support
of BP-lowering efficacy of both ultrasound RDN and radiofrequency
ablation
RADIANCE-HTN
SOLO
RADIANCE-HTN
TRIO
SPYRAL HTN-OFF
MED Pivotal
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
SPYRAL
HTN-ON MED
5
Purpose
The authors developed RADIANCE II to further study the
efficacy and safety of ultrasound RDN in the absence of
antihypertensive medications in patients with HTN.
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
6
Study Design
International,
multicenter, doubleblind sham-controlled
randomized clinical
trial
Conducted at 37
centers in the USA
and 24 in Europe
d at 37 centers in the
USA and 24 in Europe
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
Approved by local
ethics committees or
institutional review
boards and
conducted in
accordance with the
Declaration of
Helsinki
7
Patient Population
Inclusion Criteria
Exclusion Criteria
18-75 years old males and females
Unsuitable renal artery anatomy (single
functioning kidney, renal artery
stenosis, pre-existing renal stent)
Diagnosis of HTN, defined as
≥140/90mmHg but 135/85 mmHg and < 170/105mmHg AND suitable renal
artery anatomy underwent renal angiography
• Immediately underwent randomization after qualifying angiography
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
9
Interventions
• Patients were randomized 2:1
• Ultrasound RDN with the Paradise System (ReCor Medical)
• Sham procedure (renal angiography)
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
10
Intervention Follow-Up
• All patients did not take antihypertensive medications until 2 months
after randomization
• Exception: clinic BP >180/110 mmHg and home BP > 170/105
mmHg
• Received “escape antihypertensive treatment”
• Monthly visits to undergo clinic BP, HR, labs, adherence testing after 2month outcome assessment
• 7-day home BP measured prior to each onsite visit
• Medication adverse events
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
11
Outcomes
Primary Efficacy Outcome
Mean change in daytime ambulatory
SBP at 2 months
Secondary Efficacy Outcomes
Change in 24-hour ambulatory, home,
office, and daytime SBP/DBP at 2
months
Primary Safety Outcomes
Tertiary Efficacy Outcomes
All-cause mortality, kidney failure, renal
artery or vascular complications
Change at 2 months in night- time
ambulatory measurements and
ambulatory, home, and office heart rate
Hypertensive or hypotensive crisis within
30 days
Renal artery stenosis >70% at 6 months
Change in eGFR at 2 months
12
Statistical Analysis
• Utilized intention-to-treat analysis for primary and secondary
outcomes
• Also utilized a modified intention-to-treat analysis to exclude
patients that received escape antihypertensive treatment
• Assumed a 6-mmHg difference in change in daytime ambulatory SBP at
2 months between the ultrasound RDN and sham-procedure group
(standard deviation of 12 mmHg and 2-sided type I error of 5%)
• Authors estimated a sample size of 192 patients yielded a 90% power
• Enrollment of 128 patients to undergo ultrasound renal denervation
provided 95% power for the primary safety composite outcome
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
13
Baseline Characteristics
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
14
Type of Antihypertensive at Screening
Ultrasound RDN, No. (%)
n=96
Sham Procedure, No. (%)
n=51
Renin-angiotensin system
blockers
73 (76.0)
35 (68.6)
Calcium channel blockers
28 (29.2)
22 (43.1)
Diuretics
25 (26.0)
13 (25.5)
Beta-Blockers
10 (10.4)
5 (9.8)
Aldosterone antagonists
1 (1.0)
1 (2.0)
Other
3 (3.1)
3 (5.9)
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
15
Procedure
• Average ultrasound RDN procedure length = 77 minutes
• Average sham-procedure length = 44 minutes
• Successful bilateral ablation was performed in 148 of 150 patients
(98.75%)
• A total of 12 patients (8%) in the the ultrasound renal denervation
group and 10 patients (13.5%) in the sham procedure group received
antihypertensives prior to 2 months
• Of the 22 patients, 4 patients (2.7%) and 6 (8.1%), respectively,
were treated after meeting criteria for escape antihypertensive
treatment
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
16
Results
*No difference in primary safety outcome
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
17
Results
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
18
Author’s Conclusions
In patients with hypertension, ultrasound RDN reduced
daytime ambulatory SBP at 2 months in the absence of
antihypertensive medications vs. a sham procedure without
post-procedural major adverse events
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
19
Limitations
Follow-up duration
limited to 2 months
Low external validity
Difficult to predict a
patient’s BP-lowering
effect of RDN
No simple and
reproducible way to
assess sympathetically
mediated HTN prior to
ultrasound RDN
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
20
Discussion
• BP-lowering effect of ultrasound RDN was consistent over the 24-hour
circadian cycle
• Ultimately, RDN may circumvent in the consequences of…
• Variable timing of medication intake
• Forgetfulness of medication intake
• Non- adherence to oral antihypertensive
• Medications with suboptimal dosing frequency
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
21
Conclusion
• Ultrasound RDN demonstrated statistically significant reductions in
daytime ambulatory SBP and in 6 of 7 pre-specified secondary BP
outcomes compared with the sham procedure
• Outcome was achieved without any major adverse events
• Ultrasound RDN group experienced an average 7.9-mm Hg reduction in
daytime ambulatory SBP from baseline to 2 months, (a 6.3-mm Hg
greater reduction) compared with the sham procedure
Azizi M et al. The RADIANCE II Randomized Clinical Trial. JAMA. 2023;329(8):651–661
22
Endovascular Ultrasound Renal
Denervation to Treat
Hypertension (RADIANCE II)
Monaz Engineer, PharmD
PGY-2 Cardiology Pharmacy Resident
University of Chicago Medicine
July 28th, 2023
23
Example Journal Club Template
Background and Overview
Study Citation
Cite your article here using proper format.
Purpose/Background
Give a brief summary about why this study is important. You can also provide a
short background on the drug, disease state, or procedure that is being
evaluated. In addition, relevant literature on the subject can be discussed.
Study Objective
The objective, study aim or goal, should be clearly stated in the article and
copied directly so as not to change the meaning here.
Historical Context
What other related trials have been done prior to this study? Discuss any other
relevant literature on the subject here. Be sure to cite these below in the
reference list.
Methods
Study Design
Things to consider*:
○ Retrospective vs. prospective
○ Randomization
○ Blinding
○ Case control vs. RCT vs. meta-analysis
○ Superiority vs. non-inferiority
○ Multicenter vs. single site
*This is not an all-inclusive list.
Funding
Disclose funding and consider potential conflicts of interest.
Population
●
Inclusion Criteria
List the major and
noteworthy inclusion
criteria.
Exclusion Criteria
List the major and noteworthy exclusion criteria.
Give consideration to if exclusions are appropriate.
The reason does not need to be included here,
though should be a point of discussion.
This resource was developed by the ASHP New Practitioners Forum Clinical Practice Advisory Group, which is providing members the opportunity to share
resources that might assist in professional endeavors. ASHP is not responsible for, and does not officially endorse this resource, and further expressly
disclaims any and all liability for damages of any kind arising out of the use, reference to, or reliance upon any information contained in the resource. No
guarantee is provided that the content is correct, accurate, complete, up-to-date, or owned by the individual who posted it.
Copyright © 2020, American Society of Health-System Pharmacists, Inc. All rights reserved.
Interventions or Study
Procedures
Outcomes
Statistical Analysis
Describe the interventions performed in the trial. Was it active-controlled? What
was the dose of the medication(s) used? How often were they administered?
Was there a washout period for study drugs? Was there an enrollment period to
determine adherence? How were study participants randomized (i.e. 1:1, 1:2:1,
etc.)? How long was the intervention period? What was the median follow-up
time-frame? Was the follow-up period similar between the groups?
●
●
Primary outcome/endpoint:
Secondary outcomes/endpoints:
What statistical tests were used for each set of data? You should evaluate if
these tests were appropriate for your discussion, though you don’t need to
include the appropriateness of the tests here.
Did the study include a sample size calculation?
Results
Study Sample
Sample Size
How many participants
were enrolled in the study
and in each arm?
Results
●
●
●
●
●
Summary
●
Baseline Characteristics
Are they well matched between treatment groups?
Are there any noteworthy characteristics of this
sample that stand out to you?
You may include tables and/or bullet points to describe and summarize
the main results.
Be sure to include how many patients dropped out of the study and
why.
Be sure to include the results of the primary and secondary endpoints,
statistical significance (e.g. p-value, confidence interval, etc.). Consider
directing the audience to a specific table/figure within the article if
available.
Consider also including number needed to treat (NNT) or number
needed to harm (NNH).
Address noteworthy adverse event rates (if applicable).
What were the key takeaways from the trial? The key takeaways should
not include any interpretation of the results. Interpretation of the results
This resource was developed by the ASHP New Practitioners Forum Clinical Practice Advisory Group, which is providing members the opportunity to share
resources that might assist in professional endeavors. ASHP is not responsible for, and does not officially endorse this resource, and further expressly
disclaims any and all liability for damages of any kind arising out of the use, reference to, or reliance upon any information contained in the resource. No
guarantee is provided that the content is correct, accurate, complete, up-to-date, or owned by the individual who posted it.
Copyright © 2020, American Society of Health-System Pharmacists, Inc. All rights reserved.
will be included in the discussion & conclusions.
Discussion and Conclusions
Evaluation of Study
Quality
Strengths of the Study
Limitations of the Study
List them here. Examples:
large sample size, external
validity, etc.
What could be improved about the study design?
What about the trial weakens its overall impact?
(e.g. internal/external validity, statistical vs. clinical
significance, inclusion/exclusion criteria
appropriateness)
Author’s Discussion and
Conclusion
●
Summarize the author’s conclusion from the article.
Personal Discussion and
Conclusion
●
Write out your conclusions. You may reference other articles and how
findings from those might play a role in interpreting this study.
Application to Patient
Care
●
How will you use this information in practice (consider your practice site
specifically)?
References:
1. [citation for the study your journal club is focused on]
This resource was developed by the ASHP New Practitioners Forum Clinical Practice Advisory Group, which is providing members the opportunity to share
resources that might assist in professional endeavors. ASHP is not responsible for, and does not officially endorse this resource, and further expressly
disclaims any and all liability for damages of any kind arising out of the use, reference to, or reliance upon any information contained in the resource. No
guarantee is provided that the content is correct, accurate, complete, up-to-date, or owned by the individual who posted it.
Copyright © 2020, American Society of Health-System Pharmacists, Inc. All rights reserved.
Questions to Consider for your Presentation:
Background & Overview
●
●
●
What are the current guideline recommendations for this particular disease state or topic?
If applicable, how do we stratify the severity of disease being studied (i.e. A1C for patients with
diabetes, CKD stages, COPD GOLD classifications, etc.)?
If this is a new therapy, what is the biological rationale for why it might be useful for a particular disease
state?
Methods
●
●
●
●
●
●
How do the inclusion/exclusion criteria limit the population you can apply the results to?
Were the patients appropriately randomized to their treatment groups? Was there stratification in the
process?
Did the authors include a power analysis? Did enrollment achieve desired power?
Was everyone (patients, physicians, study personnel, etc.) blinded to treatments?
Was this an active controlled trial? If yes, does the active control depict the standard of care? Was it
appropriately dosed?
Was the method used to study the primary outcome appropriate? For example, if a study is assessing
agitation, was the chosen behavioral scale appropriate and validated? Have other studies assessing
similar outcomes used it?
Results
●
●
●
●
How do the baseline characteristics of the population in the study compare to the disease state being
studied?
○ Did exclusion criteria eliminate outliers and patients who may be at increased harm?
For statistically significant results, how does the NNH compare to the NNT? Are they similar, or are the
two significantly different from each other?
○ Are these results clinically significant?
Was the trial long enough to detect a difference?
Are the potential treatment benefits worth the potential harm and costs?
This resource was developed by the ASHP New Practitioners Forum Clinical Practice Advisory Group, which is providing members the opportunity to share
resources that might assist in professional endeavors. ASHP is not responsible for, and does not officially endorse this resource, and further expressly
disclaims any and all liability for damages of any kind arising out of the use, reference to, or reliance upon any information contained in the resource. No
guarantee is provided that the content is correct, accurate, complete, up-to-date, or owned by the individual who posted it.
Copyright © 2020, American Society of Health-System Pharmacists, Inc. All rights reserved.
Discussion
●
●
●
●
●
●
For your personal conclusions, would you change guideline recommendations based on the study? If so,
how? Will this study change how you practice?
Would it be feasible/appropriate to apply the study to your specific institution?
What additional limitations would you note besides the limitations described in the study?
Is the population in the study similar to patients in your practice?
Was there any bias present in the study? Who funded the study and what was the sponsor’s role in the
study?
How would you apply this to your practice?
This resource was developed by the ASHP New Practitioners Forum Clinical Practice Advisory Group, which is providing members the opportunity to share
resources that might assist in professional endeavors. ASHP is not responsible for, and does not officially endorse this resource, and further expressly
disclaims any and all liability for damages of any kind arising out of the use, reference to, or reliance upon any information contained in the resource. No
guarantee is provided that the content is correct, accurate, complete, up-to-date, or owned by the individual who posted it.
Copyright © 2020, American Society of Health-System Pharmacists, Inc. All rights reserved.
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