Iloprost for Bridging to Heart Transplantation in PH

NCT02482402 | Withdrawn Phase 2 DMC

• 2 other identifiers: IG 432013-001613-33
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Chronic Left Ventricular Failure; Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• safety and tolerability measured by adverse events rates

  The primary objective of the clinical trial is to acquire first data on safety and tolerability of inhaled Ilorpost in patients with left heart failure on the waiting list for orthotopic heart transplantation.. This proof-of-concept trial aims to evaluate the safety profile of inhaled Iloprost in this indication.

  baseline until end of study after 12 weeks

Secondary Outcomes (54)

• hemodynamics right atrial pressure

  baseline vs. 12 weeks

• hemodynamics pulmonary arterial pressure

  baseline vs. 12 weeks

• hemodynamics pulmonary arterial wedge pressure

  baseline vs. 12 weeks

• hemodynamics Cardiac output

  baseline vs. 12 weeks

• hemodynamics Cardiac index

  baseline vs. 12 weeks

Study Arms (2)

Inhaled Iloprost

EXPERIMENTAL

2 inhalations per day of 2.5 µg Iloprost \[Ventavis®\] per inhalation to a maximum of 6 inhalations per day of 5 µg Iloprost per inhalation (total daily dose 5 - 30 µg) will be performed according to each patient's health condition.

Drug: Inhaled Iloprost

Placebo inhaled

PLACEBO COMPARATOR

2 to a maximum of 6 inhalations per day of placebo solution (PLA) will be performed. Study medication will be inhaled using the portable, hand-held I-Neb AAD vibrating mesh technology nebulizer system.

Drug: Placebo

Interventions

Inhaled Iloprost DRUG

Treatment effect will be controlled at each study visit and the dose and/or inhalation frequency will be adapted.

Also known as: Ilomedin

Inhaled Iloprost

Placebo DRUG

inhalation solution placebo

Also known as: inhaled placebo

Placebo inhaled

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female and male patients of any ethnic origin with left heart insufficiency and secondary PH
• Having fulfilled his/her 18th birthday on Visit 1 (Day -7 to -1) of the study
• Written informed consent (must be available before enrollment in the trial)
• Modified WHO functional class III-IV
• PH diagnosed by right heart catheter showing:
• Baseline mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg
• Baseline pulmonary vascular resistance (PVR) \> 230 dyn x s x cm-5
• Baseline transpulmonary gradient (TPG) \> 15 mm Hg
• Echocardiogram on Visit 1/Day -7 to -1 consistent with secondary PH, specifically evidence of right ventricular hypertrophy or dilation, and absence of mitral valve stenosis
• Patients receiving maximal conventional left heart failure therapy according to current guidelines (ISHLT Guidelines 2006) including intensified treatment with diuretics and have been stable for at least 2 months before entering the study (i.e. no acute decompensations requiring i.v. diuretic treatment).
• Except for diuretics, vasodilators and antihypertensives, medical treatment should not be expected to change during the entire 12-week study period.
• Negative pregnancy test (β-HCG or urine dipstick) at the start of the trial and appropriate contraception throughout the study for women with child-bearing potential.
• Able to understand and sign the Informed Consent Form
• Ability of subject to understand character and individual consequences of the clinical trial

You may not qualify if:

• PH of any cause other than permitted in the entry criteria, e.g. concomitantly to portal hypertension, complex congenital heart disease, reversed shunt, anamestic HIV infection, suspected pulmonary veno-occlusive disease based on pulmonary oedema during a previous vasoreactivity test or on abnormal findings compatible with that diagnosis (septal lines or pulmonary edema detected previously at high resolution computer tomography), congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension
• Contraindication for right heart catheterization
• Severe lung disease: FEV1/FVC \<0.5 and total lung capacity \< 70% of the normal value
• Any subject who had received any investigational medication within 4 weeks prior to the start of this study or who is scheduled to receive another investigational drug during the course of this study
• Known intolerance to inhalation treatment
• Conditions where the effects of inhaled Iloprost on platelets might increase the risk of haemorrhage (e.g. active peptic ulcers, trauma, and intracranial haemorrhage).
• Severe coronary heart disease or unstable angina, myocardial infarction within the last six months
• Cerebrovascular events (e.g. stroke) within the last 3 months
• Active liver disease, porphyria or elevations of serum transaminases \>3 x ULN (upper limit of normal) or bilirubin \> 1.5 x ULN
• Hemoglobin concentration of less than 75 % of the lower limit of normal
• Systolic blood pressure \< 85 mmHg
• History or suspicion of inability to cooperate adequately
• Pregnancy and lactation
• History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product

Sponsors & Collaborators

• Heidelberg University: lead
• Bayer: collaborator

Study Sites (2)

Klinik für Thorax- und Kardiovaskularchirurgie

Bad Oeynhausen, 32545, Germany

Location

Thoraxclinic at the University of Heidelberg

Heidelberg, 69126, Germany

Location

MeSH Terms

Conditions

Hypertension, Pulmonary

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Ekkehard Grünig, MD

  Thoraxclinic at the University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med. Ekkehard Grünig

Study Record Dates

• First Submitted: October 31, 2014
• First Posted: June 26, 2015
• Study Start: February 1, 2015
• Primary Completion: March 17, 2015
• Study Completion: March 17, 2015
• Last Updated: December 23, 2019

Record last verified: 2019-12

Locations

DE (2)