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

NCT01627613 | Completed Phase 2 DMC

• 2 other identifiers: AP301-II-0012012-001863-64
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Lung Injury

Keywords

Peptide

Outcome Measures

Primary Outcomes (1)

• change in extravascular lung water within 7 days of treatment

  EVWL (measured with PiCCO® technique) until day 7 of treatment (AUC)

  change from baseline - day 7

Secondary Outcomes (5)

• Oxygenation index

  baseline - day 7

• ventilator plateau pressure

  baseline - day 7

• Murray Lung Injury Score

  baseline - day 7

• Ventilation parameters / lung function

  baseline - day 7

• 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))

  baseline - day 7

Study Arms (2)

AP301

EXPERIMENTAL

Treatment group

Drug: AP301

saline solution

PLACEBO COMPARATOR

Placebo group

Drug: Saline solution

Interventions

AP301 DRUG

AP301 25 mg powder for reconstitution for solution for inhalation Orally delivered doses of 87.6 mg AP301 are inhaled every 12 hours (± 30 min), for a total of 7 days.

AP301

Saline solution DRUG

Placebo solution (0.9% physiologic NaCl) is inhaled every 12 hours (± 30 min), for a total of 7 days.

saline solution

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Apeptico Forschung und Entwicklung GmbH: lead

Study Sites (1)

Department of Anesthesia, General Intensive Care and Pain Control,Medical University of Vienna

Vienna, 1090, Austria

Location

Related Publications (1)

• 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.

  PMID: 28750677 DERIVED

MeSH Terms

Conditions

Acute Lung Injury

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Roman Ullrich, Prof.

  Medical University of Vienna

  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: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2012
• First Posted: June 26, 2012
• Study Start: July 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: August 1, 2014
• Last Updated: November 18, 2019

Record last verified: 2019-11

Locations

AU (1)