Clinical trial NCT01627613: Study in Intensive Care Patients to Investigate the Clinical Effect of Repetitive Orally Inhaled Doses of AP301 on Alveolar Liquid Clearance in Acute Lung Injury
Official title: Proof of Concept Study in Male and Female Intensive Care Patients to Investigate the Clinical Effect of Repetitive Orally Inhaled Doses of AP301 on Alveolar Liquid Clearance in Acute Lung Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Lung Injury
Keywords: Peptide
Lead sponsor: Apeptico Forschung und Entwicklung GmbH
Sponsor class: INDUSTRY
First posted: 2012-06-26
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effect of orally inhaled AP301 on alveolar liquid clearance in ALI (acute lung injury) patients with the purpose to assess the treatment associated changes of extravascular lung water (EVLW) within 7 days of treatment.


Eligibility criteria: Inclusion Criteria:

* age ≥ 18
* intubated and mechanically ventilated male and female patients of the Intensive Care Units of the Department of Anesthesia, General Intensive Care and Pain Control
* meets the criteria of ALI (as defined by the American-European Consensus Conference on ALI/ ARDS):
* Onset of ALI within 48 hours
* Bilateral infiltrates seen on frontal chest radiograph
* PCWP ≤ 18 mm Hg or no clinical evidence of left atrial hypertension
* paO2/ FiO2 ratio ≤ 300 mm Hg
* EVLW in PiCCO® at screening ≥ 8 ml/PBW
* Meeting criteria for extensive hemodynamic monitoring according to investigators discretion
* ICU Patients being mechanically ventilated and are stable in this condition for at least 8 hours
* Negative pregnancy test and adequate contraception in female patients of childbearing potential
* Informed consent:
* For patients that are temporarily unable to consent (e.g. comatose patients) a subsequent informed consent has to be provided.

Exclusion Criteria:

* History of clinically relevant allergies or idiosyncrasies to AP301 or any other inactive ingredient(s) of the investigational product
* Brainstem death at screening
* Current evidence of septic shock as defined by the Surviving Sepsis Campaign (Presence of acute organ dysfunction secondary to infection plus hypotension with systolic blood pressure \< 90 mm Hg or mean arterial pressure (MAP) \< 70 mm Hg for not less than one hour which cannot be reversed with fluid resuscitation)
* Neutrophil count \<0.3 x 109 L
* Patients under immunosuppression: high dose steroids (\> 80 mg Prednisolone /d; \> 300 mg hydrocortisone / d), cancer treatment (chemotherapy or biological) or therapy with other immunosuppressive agents for organ transplantation within 2 weeks
* BMI \< 18.5 or \> 35
* Cardiogenic pulmonary edema diagnosed by echocardiography or pulmonary artery catheter
* Pregnancy / lactation or intention to fall pregnant during the time course of the study
* Women of childbearing potential as well as men of procreative capacity who are not using adequate contraception
* Participation in other interventional drug trials

Primary outcomes:
measure: change in extravascular lung water within 7 days of treatment
timeFrame: change from baseline - day 7
Secondary outcomes:
measure: Oxygenation index
timeFrame: baseline - day 7
measure: ventilator plateau pressure
timeFrame: baseline - day 7
measure: Murray Lung Injury Score
timeFrame: baseline - day 7
measure: Ventilation parameters / lung function
timeFrame: baseline - day 7
measure: Presence/absence/severity and duration of adverse effects - number and severity of adverse events (AEs), serious adverse events (SAEs) and suspected unexpected serious adverse events (SUSARs))
timeFrame: baseline - day 7
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Department of Anesthesia, General Intensive Care and Pain Control,Medical University of Vienna
Study officials:
affiliation: Medical University of Vienna
name: Roman Ullrich, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Krenn K, Lucas R, Croize A, Boehme S, Klein KU, Hermann R, Markstaller K, Ullrich R. Inhaled AP301 for treatment of pulmonary edema in mechanically ventilated patients with acute respiratory distress syndrome: a phase IIa randomized placebo-controlled trial. Crit Care. 2017 Jul 27;21(1):194. doi: 10.1186/s13054-017-1795-x.