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PVP-Guided Decongestive Therapy in HF 2

Phase 4
Recruiting
Conditions
Congestion
Heart Failure
Congestive Heart Failure
Interventions
Drug: Diuretic therapy
Registration Number
NCT06495892
Lead Sponsor
Başakşehir Çam & Sakura City Hospital
Brief 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.

Detailed 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 main hypothesis is as follows: A simple assessment of peripheral venous pressure (PVP) will better guide the diuretic need and long-term outcomes (all-cause mortality, all cause re-hospitalization, emergency department visits) compared to standard evaluation.

III. METHODS

1. Application for Institutional Review Board (IRB)/Ethics board approval The study will be at participating centers. An IRB/Ethics board approval has been obtained from Marmara University, Pendik Training and Research Hospital local ethics board.

2. Study population Patients 18-99 years old who were admitted with a de novo or decompensated chronic HF and accept to participate in the study 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 withdraw their 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. Data Collection The study will start at participating centers on July 1, 2024.

Baseline variables Baseline variables will be entered to the electronic study form (RedCap).

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 via RedCap randomization module. The details of demographic characteristics, symptoms, physical examination findings and drug list will be noted to a standard electronic study form (see appendix). A routine electrocardiogram and echocardiogram will be performed at the earliest convenience.

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 and modified Valsalva maneuver. 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 or Valsalva 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 veno-venous 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 ESC guidelines (see references). In the 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. This information on these outcomes will be obtained from the national electronic database. The follow-up duration is planned to be limited to one year.

Predefined secondary analyses

There will be subanalyses from the same cohort, 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, renal injury, 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 hospitalizations.

* Usual patterns of diuretic use

Estimated number of subjects to be submitted:

We estimated that the enrollment of 621 participants would provide the study with a statistical power of 95% to detect a relative risk reduction of 26% (hazard ratio \[HR\] = 0.74) for the composite primary outcome (PVP-guided group: 40%, standard approach: 50%), using a two-sided test at the 0.05 significance level. This calculation assumes a 10% censoring rate and a 1-year follow-up period. The weighted event rate (πe=45%) was used to estimate the required number of events. To account for potential loss to follow-up and ensure robust analysis, the sample size was increased to 650 participants, maintaining equal allocation between groups (1:1 randomization).

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 and student t-test, as appropriate. 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 SPSS (version 24.0; SPSS Inc., Chicago, IL) and MedCalc Software (version 18.2.1 \[Evaluation version\]; MedCalc Software, Ostend, Belgium).

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
650
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PVP-GuidedDiuretic therapyPeripheral venous pressure guided diuretic therapy arm
ControlDiuretic therapyStandard dıuretic therapy arm
Primary Outcome Measures
NameTimeMethod
Primary end point: Major adverse events (Mortality and rehospitalization)One year

The difference in the combined rate of all-cause mortality, all-cause hospitalization and all-cause emergency department visits

Secondary Outcome Measures
NameTimeMethod
Secondary combined end point:Major cardiac adverse events (Cardiac mortality and hospitalization)One year

The difference in the combined rate of cardiovascular mortality, HF-related hospitalization, HF-related emergency department visits.

Trial Locations

Locations (16)

Ankara Etlik City Hospital

🇹🇷

Ankara, Turkey

Antalya Atatürk State Hospital

🇹🇷

Antalya, Turkey

Akdeniz University

🇹🇷

Antalya, Turkey

Trakya University

🇹🇷

Edirne, Turkey

Erzurum Atatürk University Hospital

🇹🇷

Erzurum, Turkey

Eskişehir City Hospital

🇹🇷

Eskişehir, Turkey

Mehmet Akif Ersoy Training and Research Hospital

🇹🇷

Istanbul, Turkey

Basaksehir Cam and Sakura City Hospital

🇹🇷

Istanbul, Turkey

Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital

🇹🇷

Istanbul, Turkey

Bağcılar Training and Research Hospital

🇹🇷

Istanbul, Turkey

Bakırçay University, Faculty of Medicine

🇹🇷

Izmir, Turkey

Pazarcık State Hospital

🇹🇷

Kahramanmaraş, Turkey

Kafkas University Health Research and Application Hospital

🇹🇷

Kars, Turkey

Kütahya Health Sciences University

🇹🇷

Kütahya, Turkey

Tokat Gaziosmanpaşa University

🇹🇷

Tokat, Turkey

İdil State Hospital

🇹🇷

Şırnak, Turkey

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