Viewing Study NCT02482402



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Last Modification Date: 2024-10-26 @ 11:45 AM
Study NCT ID: NCT02482402
Status: WITHDRAWN
Last Update Posted: 2019-12-23
First Post: 2014-10-31

Brief Title: Iloprost for Bridging to Heart Transplantation in PH
Sponsor: Heidelberg University
Organization: Heidelberg University

Study Overview

Official Title: Iloprost for Bridging to Heart Transplantation in Patients With Pulmonary Hypertension and Left Heart Failure A Randomized Controlled Double-blind Parallel Group Proof-of-concept Trial
Status: WITHDRAWN
Status Verified Date: 2019-12
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Delay in recruitment
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: BRIDGE
Brief Summary: Trial Rationale Justification To assess efficacy and safety of inhaled Iloprost in treatment naïve patients with left heart failure and pulmonary hypertension who are on the waiting list for orthotopic heart transplantation As patients often show increasing hemodynamic values while waiting for a donor organ the transplantation becomes infeasible at the time of identification of an appropriate donor organ when reaching the exclusion limits Therefore there is a high need of improvement and stabilisation of the patients hemodynamic values as PVR PAP and TPG In a retrospective non-controlled study inhaled Iloprost has already shown a beneficial effect on the hemodynamics as reduction of PVR TPG and CI Schulz 2010 Treatment with inhaled Iloprost could stabilize the hemodynamics and prevent the patients from being classified as ineligible by the time an appropriate donor organ is identified

However the adverse event profile regarding frequency time-dependency has to be further validated to show safety and tolerability of inhaled Iloprost in this indication

All patients can be transferred to a long-term medically supervised observation period with inhaled Iloprost therapy
Detailed Description: Scientific Background In many patients with severe left heart failure LHF a chronic pulmonary hypertension PH occurs during follow-up leading to a remodeling of pulmonary arteries with an increase in pulmonary artery pressure PAP pulmonary vascular resistance PVR and transpulmonary gradient TPG According to the International Society for Heart and Lung Transplantation and the German Standing Committee on Organ Transplantation cardiac transplantation is contraindicated if values of PAP PVR andor TPG are above 40 mmHg 240 dyn x s x cm-5 and 15 mmHg respectively Even if the patients show only slightly elevated hemodynamic values at the time of application for transplantation values most often reach the respective exclusion limits during the waiting period Patients signed in for transplantation partially are not any longer electable for orthotopic heart transplantation OHT at the time of identification of an appropriate donor organ In the meantime the time on the waiting list for heart transplantation is increasing In 2001 patients being on the waiting list were undergoing heart transplantation within one year In contrast 972 patients were on the waiting list while only 325 heart transplantations were performed in Germany in 2011 wwweurotransplantnl

At present no specific therapy for PH due to left heart disease is available Galie 2009 treatment with PAH agents is not recommended due to lack of data Rosenkranz 2011

There are only few studies with PH-targeted medication within this indication Phosphodiesterase inhibitors eg Sildenafil Endothelin-receptor antagonists and Prostacyclin are potential agents for the treatment of PH during the waiting period for a heart transplantation

Iloprost is a synthetic analogue of Prostacyclin PGI2 Iloprost dilates systemic and pulmonary arterial vascular beds leading to a reduction of blood pressure

In a previous study the investigators administered aerosolized Iloprost ILO in 14 patients with pulmonary hypertension due to chronic cardiac failure on the waiting list for heart transplantation Iloprost caused a significant reduction in pulmonary arterial pressure and pulmonary vascular resistance without severe side effects and was more effective than nitric oxide Sablotzky Grünig et al 2002 2003 In a retrospective non-controlled study in 51 patients awaiting orthotopic heart transplantation Iloprost inhalation caused a significant decrease in PVR from 458 dyn x s x cm-5 to 345 dyn x s x cm-5 a significant decrease in TPG 21 mmHg to 17 mmHg and a significant improvement in Cardiac Index CI from 209 lminm2 to 223 lminm2 Schulz et al 2010 In a retrospective non-controlled study low-dose Bosentan improved hemodynamic parameters and 1-year survival rate in 82 end-stage heart failure patients on the waiting list for cardiac transplantation Hefke et al 2011

Randomized-controlled trials are missing within this indication Sildenafil is not a medication of first choice due to contraindications and as well as many patients waiting for OHT are treated with nitrate medication due to coronary heart disease In contrast inhaled Iloprost has advantageous effects on coronary perfusion However in this indication the adverse event profile of inhaled Iloprost regarding frequency and time-dependency is not yet clear In Germany inhaled Iloprost is administered by the I-Neb AAD-System which allows precise reproducible dose of the drug

Due to the positive results in retrospective analyses and in the treatment of patients with pulmonary hypertension the initiation of this proof-of-concept study seems to be justified

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: None
Is a FDA Regulated Device?: None
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None
Secondary IDs
Secondary ID Type Domain Link
2013-001613-33 EUDRACT_NUMBER None None