Clinical trial NCT00742482: Efficacy and Safety of 3 Doses of HL10 Given at Fixed Time Intervals Compared to Standard Therapy
Official title: A Phase III Study With Freeze Dried HL10, Three Dosages of 200 mg/kg Ideal Body Weight Versus Standard Therapy in ALI/ARDS Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Acute Lung Injury
Acute Respiratory Distress Syndrome
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2008-08-27
Enrollment: 418
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 the study is to evaluate the efficacy and safety of three doses of HL 10 given at fixed time intervals compared to standard therapy


Eligibility criteria: Inclusion Criteria:

* Patients intubated and on mechanical ventilation
* Patients with Acute Lung Injury defined as (a, b, c and d are all applicable): a: PaO2/FiO2 \< or equal to 300 mmHg (40.0 kPa) (regardless of PEEP level), b: Acute onset, c: Pulmonary artery wedge pressure \< or equal to 18 mmHg when measured or no clinical evidence of left atrial hypertension, d: Bilateral infiltrates seen on frontal chest radiograph
* Less than 60 hours from onset of the present period of mechanical ventilation to 1st instillation
* Expected to continue on mechanical ventilation for more than 24 hours
* 18 years of age or older
* Following receipt of verbal and written information about the trial, the patient or legally acceptable representative must provide signed and dated informed consent before any trial related activity is carried out

Exclusion Criteria:

* Current diagnosis of acute bronchial asthma attack
* History of or clinical suspicion of lung fibrosis
* Current diagnosis of suspected pulmonary thrombo-embolism
* Patients on daily medication for chronic obstructive pulmonary disease at time of admission to ICU
* Patients who have received mechanical ventilation for more than 48 hours continuously within 1 month prior to the present period of mechanical ventilation
* Patients with pneumonectomy or lobectomy
* Patients with untreated pneumothorax at time of instillation
* Patients having tracheostomy at time of instillation
* Patients who have had surgical procedures under general anaesthesia performed within 6 hours prior to inclusion blood gas sample
* Patients having mean arterial blood pressure \< 50 mmHg in spite of adequate fluid administration and/or vasoactive drugs at time of instillation
* Patients having PaO2 \< 75 mmHg with a FiO2 = 1.0 not responding to adjustment of PEEP at time of instillation
* Glasgow Coma Score \< or equal to 10 before sedation or major findings on CT/MR scan of the head such as: brain oedema, acute space occupying lesion, other acute lesions with bleeding or mass effect (patients with minor lesion which do not require further diagnostics or monitoring can be included)
* Patients with life expectancy less than 3 months due to primary disease assessed by the attending physician (e.g., end-stage cancer, AIDS or generally poor health)
* Known or suspected hypersensitivity to constituents(s) of the investigational product
* Patients who have received treatment with any investigational drug within the previous 4 weeks
* Current participation in any other interventional clinical trial until day 29 of the trial
* Patients previously randomised in this trial
* Patients known or suspected of not being able to comply with a study protocol (e.g., due to alcoholism, drug dependency or psychotic state)
* Females of childbearing potential who have a positive pregnancy test or who are breast feeding
* Patients suffering from highly infectious diseases where trial related procedures could pose a safety risk for the staff (e.g., SARS)

Primary outcomes:
measure: 28 days mortality
timeFrame: 28 days
Secondary outcomes:
measure: Days alive and off ventilator
timeFrame: Day 29
measure: Days on ventilation
timeFrame: Day 1 to Day 29
measure: Days alive and out of ICU
timeFrame: Day 29
measure: Changes in Pao2/FiO2 ratios and other relevant lung parameters, changes in SOFA score
timeFrame: From Day 1 to Day 4, Day 1 to Day 8, Day 4 to Day 8
measure: Dead/alive at discharge of ICU
timeFrame: Followed until Day 180
measure: Dear/alive at discharge from hospital
timeFrame: Followed until Day 180
measure: 180 days mortality
timeFrame: 180 days
Other outcomes:
Locations:
city: Wien
country: Austria
facility: Allgemeines Krankenhaus, Klinik für Anästhesie un Allgemeine Intensivmedizin
city: Brussels
country: Belgium
facility: Erasme University Hospital
city: Toronto
country: Canada
facility: Mount Sinai Hospital, Critical Care Unit
state: Ontario
city: Odense C
country: Denmark
facility: Odense University Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital, Intensive Care Unit
city: Paris
country: France
facility: Hôpital Pitié Salpétrière, Département d'Anesthésie Réanimation
city: Aachen
country: Germany
facility: Klinik für Anästhesiologie der RWTH Aachen
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Utrecht
country: Netherlands
facility: Department of Intensive Care Medicine
city: Oslo
country: Norway
facility: Ullevål University Hospital, INtensive Care Department
city: Sabadell (Barcelona)
country: Spain
facility: Consorci Hospitalari Parc Taulí
city: Lund
country: Sweden
facility: University Hospital of Lund, Department of Intensive Care
city: London
country: United Kingdom
facility: St Thomas Hospital, Adult Intensive Care
Study officials:
affiliation: Anaesthesist-Intensivist, Department of Intensive Care Medicine
name: Jozef Kesecioglu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lu Q, Zhang M, Girardi C, Bouhemad B, Kesecioglu J, Rouby JJ. Computed tomography assessment of exogenous surfactant-induced lung reaeration in patients with acute lung injury. Crit Care. 2010;14(4):R135. doi: 10.1186/cc9186. Epub 2010 Jul 15.
citation: Kesecioglu J, Beale R, Stewart TE, Findlay GP, Rouby JJ, Holzapfel L, Bruins P, Steenken EJ, Jeppesen OK, Lachmann B. Exogenous natural surfactant for treatment of acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2009 Nov 15;180(10):989-94. doi: 10.1164/rccm.200812-1955OC. Epub 2009 Aug 27.