Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05217342 |
| Other study ID # |
MU-2022-001 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2022 |
| Est. completion date |
January 1, 2024 |
Study information
| Verified date |
March 2023 |
| Source |
Marmara University |
| Contact |
Emre K Aslanger, Assoc. Prof. |
| Phone |
+905325109796 |
| Email |
mr_aslanger[@]hotmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The investigators hypothesize that a simple assessment of peripheral venous pressure (PVP)
will better predict the diuretic need and long-term outcomes (all cause mortality, all cause
rehospitalization, emergency department visits) compared to standard evaluation.
Description:
I. BACKGROUND AND SIGNIFICANCE
Precise assessment of volume status is essential in diagnosis and management of diuretic
therapy in patients hospitalized for heart failure (HF). Unfortunately, no clear guidelines
are present for in-hospital management of congestion. Consequently, nearly half of the
patients hospitalized for congestive HF are discharged with persistent congestion. This
contributes to high rates of readmission and mortality.
Recently, it has been shown that a simple assessment of peripheral venous pressure (PVP)
demonstrates a high correlation with central venous pressure (CVP), indicating that PVP may
be useful in the standard bedside clinical assessment of volume status in HF patients to help
guiding decongestive therapy.
II. THE HYPOTHESIS
The investigators hypothesize that a simple assessment of peripheral venous pressure (PVP)
will better predict the diuretic need and long-term outcomes (all cause mortality, all cause
rehospitalization, emergency department visits) compared to standard evaluation.
III. METHODS
1. Application for Institutional Review Board (IRB)/Ethics board approval The study will be
conducted at Marmara University, Pendik Training and Research Hospital, Cerrahpaşa
University Hospital, Darıca Farabi Training and Research Hospital, Dr. Siyami Ersek
Thoracic and Cardiovascular Surgery Training and Research Hospital, and Başaksehir Çam &
Sakura Hospital, all of which are tertiary referral centers for heart failure. An
IRB/Ethics board approval will be obtained from the local ethics boards.
2. Study population Patients >18 years old who were admitted with a de novo or
decompensated chronic HF will be enrolled. Patients will be included regardless of
ejection fraction or etiology of HF, but these will be noted as baseline variables. All
patients or legal surrogate decision makers will be requested to provide a written
informed consent prior to enrollment. Patients who does not consent, those with upper
extremity venous pathology, those with a baseline creatinine level equal to or above 3.5
mg/dL, those with severe stenotic valvular disease and hypertrophic cardiomyopathy will
be excluded.
3. Centers and Personnel The study will be undertaken at Marmara University, Pendik
Training and Research Hospital, Cerrahpaşa University Hospital, Darıca Farabi Training
and Research Hospital, Başaksehir Çam & Sakura Hospital and Dr. Siyami Ersek Thoracic
and Cardiovascular Surgery Training and Research Hospital.
4. Data Collection The study will start at Marmara University, Pendik Training and Research
Hospital, Başaksehir Çam & Sakura Hospital, Cerrahpaşa University Hospital, Darıca
Farabi Training and Research Hospital and Dr. Siyami Ersek Thoracic and Cardiovascular
Surgery Training and Research Hospital, at January 1, 2022 (after the approvals from the
local ethical committees are obtained).
Baseline variables Baseline variables will be collected via chart review and entered to the
study form (see below).
Procedures A peripheral intravenous (IV) access, using an 18 to 22-gauge IV line, will be
placed preferably to an upper extremity vein before enrollment. This line will be used to
draw blood samples first. After blood samples were collected the subjects will be randomized
to standard or PVP guided therapy groups. Randomization will be done using a
computer-generated random allocation list. The details of demographic characteristics,
symptoms, physical examination findings and drug list will be noted to a standard study form
(see below).
A routine electrocardiogram and echocardiogram (including stroke volume calculated form left
ventricular outflow tract size and velocity-time integral; diastolic mitral flow Doppler and
mitral annular tissue Doppler measurements, inferior vena cava diameter and respiratory
variation) and an 8-point lung ultrasound for total B-line count will be performed at the
earliest convenience and before discharge.
After the blood samples were collected, line will be flushed carefully. PVP will be obtained
by transducing a peripheral intravenous line after zeroing at the phlebostatic axis. The
phlebostatic axis will be accepted as the midpoint between the anterior and posterior
surfaces of the chest at the level of the fourth intercostal space meets with sternum, which
is assumed to be correlated with the mid-level of the right atrium. The patient's arm will be
placed parallel to the patient such that the position of the peripheral IV to be at the
phlebostatic axis. Continuity of the peripheral IV line with the central venous system will
be confirmed by demonstrating augmentation of the venous pressure waveform using manual or
tourniquet circumferential occlusion of the extremity proximal to the catheter. If the
pressure waveform failed to augment appropriately, data will not be collected, and the
patient will be documented for study purposes as a technique failure. Daily fluid intake and
output, weight, and biochemistry measurements, as required, will be done.
The patients in whom the first and the predischarge PVP cannot be measured due to technical
issues (unable to provide upper extremity IV access, unable to confirm augmentation test)
will be excluded from the study. Also, the patients requiring in-hospital intubation,
high-dose inotrope or vasopressor infusion (≥10 mcg.kg-1.min-1 dopamine, dobutamine or
equivalent), intraaortic balloon support, dialysis or venovenous ultrafiltration will be
excluded from the study (but these patients will be included in the in-hospital analyses).
In hospital diuretic treatment will be guided by European Society of Cardiology guidelines
(see below for algorithm). In standard therapy arm, the treatment and the decision of
discharge will be left to physicians' discretion. In the PVP-guided arm, a PVP ≤9 mmHg will
be targeted before discharge.
Outcomes The primary outcome of the study is the composite endpoint of all-cause mortality,
all-cause hospitalization and all-cause emergency department visits. The secondary outcomes
will include cardiovascular mortality, HF-related hospitalization, HF-related emergency
department visits. These information on these outcomes will be obtained from national
electronic database. The follow-up duration is planned to be limited to one-year.
Summary of patient enrollment criteria
Inclusion criteria
- Hospitalization for heart failure (de novo or decompensated chronic heart failure)
- Age >18
Exclusion criteria
- A prior history of upper extremity venous disease
- Serum creatinine ≥ 3.5 mg/dL
- Severe stenotic valvular disease
- Hypertrophic obstructive cardiomyopathy
Exclusion from long term follow-up after randomization
- Unable to obtain first and pre-discharge PVP due to technical issues (unable to access
an upper extremity vein, negative augmentation test)
- In-hospital intubation
- Need for high-dose vasopressor or inotrope medications (≥10 mcg.kg.-1.min-1 dopamine,
dobutamine or equivalent)
- Need for intra-aortic balloon pump support
- In-hospital need for dialysis or veno-venous ultrafiltration
Predefined secondary analyses
There will be substudies from the same cohort utilizing other analyses, as defined below:
- The correlation between predischarge PVP and long-term outcomes. A multivariable
analysis will also be executed for predicting the primary end point.
- The correlation between the change in PVP during hospital stay and long-term outcomes. A
multivariable analysis will also be executed for predicting the primary end point.
- The correlation between the change in PVP during hospital stay and worsening renal
function, need for dialysis or veno-venous ultrafiltration.
- The comparison of the two arms in terms of worsening renal function, need for dialysis
or veno-venous ultrafiltration.
- The comparison of the two arms in terms of EVEREST congestion score.
- The comparison of the two arms in terms of the days in hospital.
- The comparison of the two arms in terms of the number of repeat hospitalization.
- The relationship between venous compliance and short and long-term outcomes.
Estimated number of subjects to be submitted:
It is estimated that the enrollment of 586 participants would provide the study with a
statistical power of 95% to detect a relative excess rate of 10% in primary outcome
(peripheral pressure guided group 20% versus standard approach 30%) with the use of a
two-sided test at the 0.05 level. Accordingly, it is expected to enroll at least 600 patients
in a one-year enrollment period.
Statistical Analysis Baseline characteristics will be summarized using standard descriptive
statistics. Comparisons of relevant parameters between groups will be performed by
chi-square, Fisher's exact test, Mann-Whitney U, Kruskal-Wallis H test, one-way ANOVA and
student t-test, as appropriate. Patients with missing values will be excluded pairwise from
analyses. Kaplan-Meier analysis will be performed to determine the cumulative long-term
mortality and composite outcome rates in subgroups. The mortality across groups will be
compared using log-rank test. A Cox-regression model will be used to perform a survival
analysis according to pre-discharge peripheral venous pressure and composite outcome.
Baseline characteristics with a P value of 0.05 or less in the univariate analysis will be
included and a step-down procedure will be applied for selection of final covariates.
Statistical analyses will be performed with Statistical Package for Social Sciences (SPSS,
version 24.0; SPSS Inc., Chicago, IL) and MedCalc Software (version 18.2.1 [Evaluation
version]; MedCalc Software, Ostend, Belgium).
