Peripheral Venous Pressure-Guided Decongestive Therapy in Heart Failure 2
Phase: PHASE4
Conditions: Heart Failure, Congestion, Congestive Heart Failure
Sponsor: Başakşehir Çam & Sakura City Hospital

P V P- G ui d e d D e c o n g e sti v e T h er a p y i n H F 2 ( P E RI P H E R A L- H F 2)
N C T 0 6 4 9 5 8 9 2
N C T 0 6 4 9 5 8 9 2
J ul y 1, 2 0 2 4
PVP-Guided Decongestive Therapy in HF 2 
(PERIPHERAL-HF2)
NCT06495892
July 2nd, 2021

Study Title: Peripheral Venous Pressure-Guided Decongestive Therapy in Heart Failure 2 
Short title: PERIPHERAL-HF2 
Emre Aslanger, MD, Prof. 
Health Sciences University, Başakşehir Pine and Sakura City Hospital 
Department of Cardiology 
Istanbul, Turkey 
Özlem Yıldırımtürk, MD, Prof. 
Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital 
Division of Cardiology 
Istanbul, Turkey 

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 
 
We 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 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. Centers and Personnel  
The study will be undertaken at Health Sciences University, Başakşehir Pine and Sakura City 
Hospital, Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research 
Hospital, and other participating centers. The complete list is as follows:  
1, Ankara Etlik City Hospital, Principal investigator: Belma Kalaycı, Çağatay Tunca 
2, Antalya Atatürk State Hospital, Principal investigator: Özgür Çağaç 
3, Akdeniz University, Faculty of Medicine, Principal investigator: Nagehan 
Küçükler 
4, Bağcılar Training and Research Hospital, Principal investigator: Esra Dönmez, 
Researcher: Sevgi Özcan 
5, Bakırçay University, Faculty of Medicine, Çiğli Training and Research Hospital, 
Principal investigator: Saadet Aydın 
6, Başakşehir Pine and Sakura City Hospital, Principal investigator: Emre 
Aslanger, Researchers: Ahmet İlker Tekkeşin, Funda Özlem Pamuk, Yelda Saltan  
7, Çanakkale Onsekiz Mart University, Faculty of Medicine, Principal investigator: 
Hakkı Kaya 
8, Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research 
Hospital, Principal investigator: Özlem Yıldırımtürk 
9, Eskişehir City Hospital, Principal investigator: Ezgi Çamlı Babyiğit 
10, Erzurum Training and Research Hospital, Principal investigator: Oğuzhan 
Birdal 
11, İdil State Hospital, Principal investigator: Barış Güven 
12, Kafkas University Health Research and Application Hospital, Principal 
investigator: Doğan İliş 

13, Kartal Koşuyolu High Specialization Education and Research Hospital, 
Principal investigator: Süleyman Çağan Efe 
14, Kütahya Health Sciences University, Faculty of Medicine, Principal 
investigator: Taner Şen, Mevlüt Demir 
15, Mehmet Akif Ersoy Training and Research Hospital, Principal investigator: Ali 
Kemal Kalkan 
16, Pazarcık State Hospital, Principal investigator: Orhan Karaca 
17, Tokat Gaziosmanpaşa University, Faculty of Medicine, Principal investigator: 
Çağrı Zorlu 
18, Trakya University, Faculty of Medicine, Principal investigator: Cihan Öztürk 
 
4. Data Collection 
The study will start at participating centers on July 15, 2024. 
 
Baseline variables 
Baseline variables will be collected via chart review and entered to the electronic 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 electronic study form (see 
below). 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. 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 below for algorithm). 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.   
 
Summary of patient enrollment criteria 

 
Inclusion criteria 
- 
Hospitalization for heart failure (de novo or decompensated chronic heart failure) 
irrespective of left ventricular ejection fraction  
- 
Age 18-99  
- 
Accept to participate 
 
Exclusion criteria 
- 
A prior history of upper extremity venous disease  
- 
Serum creatinine ≥ 3.5 mg/dL  
- 
Severe stenotic valvular disease  
- 
Hypertrophic obstructive cardiomyopathy  
- 
Withdrawal of consent 
 
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 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 
- 
The derivation and validation of an algorithm regarding the use of diuretic dose and 
peripheric venous pressure will also be aimed. It will be derived and validated in the 
first and second half of the study, respectively. 
 
Estimated number of subjects to be submitted:  
We 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, we expect 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 SPSS (version 24.0; SPSS Inc., Chicago, IL) and MedCalc Software 
(version 18.2.1 [Evaluation version]; MedCalc Software, Ostend, Belgium). 
   
 
 
 
 
 

Study form 
 
 
 

 
TR: 
TR: