Improving treatment of right ventricular failure in pulmonary hypertension patients.

Phase 2

Conditions: High pulmonary blood pressure
Pulmonary hypertension
10019280
10037454

Registration Number: NL-OMON46099

Lead Sponsor: Vrije Universiteit Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Patients should be diagnosed with pre-capillary pulmonary hypertension either PAH or CTEPH, have clinical signs of decompensated right heart failure, and needing hospital - or ICU admission for IV diuretics.
• PAH (group 1 and 1*) or CTEPH (group 2), diagnosed according ESC/ERS guidelines;
o Mean Pulmonary Artery Pressure (mPAP) >= 25 mmHg
o Pulmonary Arterial Wedge Pressure (PCWP) <15 mmHg
o Other possible causes of PH are excluded
• 18-70 years old
• Increased body weight despite increased dose diuretics in past month
• Clinical signs of decompensation: ankle edema and/or ascites
• eGFR; 30 ml/min/1.73m2
• Sinusrhythm

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study:
• Pulmonary hypertension due to connective tissue disease, and PH due to left heart disease (group 2).
• Hypoxia defined as SaO2 <=80% and/or <= 90% with oxygen suppletion.
• Pregnancy, lactation
• Anuria (urine production <50 ml/day)
• Known intolerance of loop diuretics or terlipressin
• Recent diagnosis (<1 month ago) of acute pulmonary embolism
• Underlying infectious disorder/ bacteremia
• Known history of occlusive arterial disease (e.g. coronary artery disease) and/or peripheral artery disease, exception: pulmonary embolism
• Type 1 and type 2 diabetes mellitus
• Chronic use of NSAIDs
• Pre-existing renal failure from other causes than forward failure (eg diabetes)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The aim of this study is: To explore efficacy and safety of terlipressin as<br /><br>add on therapy to loop diuretics in patients with pre-capillary pulmonary<br /><br>hypertension who are hospitalized for right ventricular failure. Change in<br /><br>creatinine after 48 hours, is considered as a primary safety endpoint.<br /><br>Endpoint assessment will be after 48 hours and when, in opinion of the<br /><br>clinician an optimal volume status of the patient is reached. Primary efficacy<br /><br>endpoint will be weight loss over the first 48 hours after start of drug<br /><br>administration. This study is considered positive when: The weight loss after<br /><br>48h is higher in the terlipressin treated patients and change in creatinine is<br /><br>smaller or not significantly increased compared to patients who are treated<br /><br>with loop diuretics alone. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Other study parameters and endpoints are:<br /><br>• Fluid balance (= Fluid intake - urine output) after 48h<br /><br>• Kidneyfunction after 48h<br /><br>• Urine output after 48h<br /><br>• Final dose of loop diuretics at 48h<br /><br>• Time interval from treatment start to accomplishing an optimal volume status/<br /><br>time to dismissal<br /><br>• Change in creatinine at t = 48h, t = 72h and at dismissal<br /><br>• N-terminal brain-type natriuretic peptide (NT-proBNP) levels<br /><br>• Total weight loss at t= 72h and dismissal<br /><br>• Total urine output at dismissal<br /><br>• Need for additional treatment (in both treatment arms)</p><br>