Condition category
Respiratory
Date applied
06/09/2010
Date assigned
23/09/2010
Last edited
23/01/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Danny Francis McAuley

ORCID ID

Contact details

Microbiology Building
Royal Victoria Hospital
Grosvenor Road
Belfast
BT12 6BN
United Kingdom

Additional identifiers

EudraCT number

2010-021186-70

ClinicalTrials.gov number

Protocol/serial number

10089DMCA-CS

Study information

Scientific title

Keratinocyte growth factor in acute lung injury to reduce pulmonary dysfunction: a randomised placebo controlled trial

Acronym

KARE

Study hypothesis

The hypothesis is that treatment with palifermin will improve surrogate clinical outcomes in adult patients with acute lung injury and is safe.

On 23/01/2014 the trial design was changed from 'Prospective randomised double-blind placebo-controlled phase II single-centre trial' to 'Prospective randomised double-blind placebo-controlled phase II multi-centre trial'

Ethics approval

Office for Research Ethics Committees Northern Ireland (ORECNI) HSC REC 2, 04/08/2010, ref: 10/NIR02/32

Study design

Prospective randomised double-blind placebo-controlled phase II multi-centre trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Acute lung injury

Intervention

Patients will be randomised to palifermin 60 µg/kg or normal saline placebo daily as a bolus intravenous injection for up to 6 days. Administration will not occur through an intravenous line that has been flushed with heparin. The intravenous line will be flushed with normal saline prior to and after study drug administration. The first dose of study drug will be administered within 4 hours of randomisation and subsequent doses will be at 10 am daily starting on the following calendar day.

Intervention type

Drug

Phase

Phase II

Drug names

Palifermin

Primary outcome measures

Oxygenation index (OI) at day 7 or the last available OI prior to patient discontinuation from the study. OI is a physiological index of the severity of ALI and measures both impaired oxygenation and the amount of mechanical ventilation delivered. We and others have shown OI is independently predictive of mortality in patients with ALI. We have chosen day 7 as we expect this time interval will minimise the competing effects of death and extubation, while allowing a sufficient time interval for a biological effect to occur.

OI is calculated as (mean airway pressure [cm H20] x FiO2 x 100) = PaO2 (kPa). These simple measurements are easily and routinely collected as part of standard ventilator practice.

Secondary outcome measures

1. Oxygenation index (OI) at days 3 and 14
2. Physiological indices of acute lung injury, as measured by respiratory compliance (Crs), P/F ratio, and the pulmonary dead space fraction at days 3, 7 and 14
3. Change in sequential organ failure assessment (SOFA) score from baseline to day 7 and 14
4. Safety and tolerability as assessed by the occurrence of AEs and Suspected Unexpected Serious Reactions (SUSARs)

Although the duration of ventilation and ICU stay as well as ICU and hospital mortality and 28-day mortality will also be documented, these important clinical outcomes are not included as major outcome measures as the study is not adequately powered to assess these outcomes.

Overall trial start date

10/09/2010

Overall trial end date

31/12/2013

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 23/01/2014:
1. Aged greater than 18 years, either sex
2. Acute lung injury (ALI) as defined by acute onset of:
2.1. Hypoxic respiratory failure (partial pressure of oxygen in arterial blood [PaO2]/fraction of inspired oxygen [FiO2] less than or equal to 40 kPa)
2.2. Bilateral infiltrates on chest X-ray consistent with pulmonary oedema
2.3. No clinical evidence of left atrial hypertension or if measured, a pulmonary arterial occlusion pressure (PAOP) less than or equal to 18 mmHg
2.4. Requirement for positive pressure mechanical ventilation via an endotracheal tube or tracheostomy
All ALI criteria above must occur within the same 24-hour period. The onset of ALI is when the last ALI criterion is met. Patients must be enrolled within 72 hours of ALI onset.

Previous inclusion criteria:
1. Aged greater than 18 years, either sex
2. Acute lung injury (ALI) as defined by acute onset of:
2.1. Hypoxic respiratory failure (partial pressure of oxygen in arterial blood [PaO2]/fraction of inspired oxygen [FiO2] less than or equal to 40 kPa)
2.2. Bilateral infiltrates on chest X-ray consistent with pulmonary oedema
2.3. No clinical evidence of left atrial hypertension or if measured, a pulmonary arterial occlusion pressure (PAOP) less than or equal to 18 mmHg
2.4. Requirement for positive pressure mechanical ventilation via an endotracheal tube or tracheostomy
All ALI criteria above must occur within the same 24-hour period. The onset of ALI is when the last ALI criterion is met. Patients must be enrolled within 48 hours of ALI onset.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

60

Participant exclusion criteria

Current exclusion criteria as of 23/01/2014:
1. Aged less than 18 years
2. More than 48 hours from the onset of ALI
3. Pregnancy
4. Participation in a clinical trial of an investigational medicinal product within 30 days
5. Consent declined
6. Current treatment with KGF
7. Known hypersensitivity to palifermin or Escherichia coli derived proteins
8. Previous adverse reaction to palifermin
9. Active history of malignancy excluding haematological malignancies
10. Chronic liver disease with Child-Pugh score greater than 12

Previous exclusion criteria:
1. Aged less than 18 years
2. More than 48 hours from the onset of ALI
3. Pregnancy
4. Participation in a clinical trial of an investigational medicinal product within 30 days
5. Consent declined
6. Current treatment with KGF
7. Patients with pancreatitis
8. Known hypersensitivity to palifermin or Escherichia coli derived proteins
9. Previous adverse reaction to palifermin
10. History of active malignancy
11. Chronic liver disease with Child-Pugh score greater than 12

Recruitment start date

10/09/2010

Recruitment end date

31/12/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Microbiology Building
Belfast
BT12 6BN
United Kingdom

Sponsor information

Organisation

Belfast Health and Social Care Trust (UK)

Sponsor details

c/o Professor Ian Young
Trust Research Office
2nd Floor King Edward Building
Royal Victoria Hospitals
Grosvenor Road
Belfast
BT12 6BA
United Kingdom

Sponsor type

Government

Website

http://www.belfasttrust.hscni.net/

Funders

Funder type

Government

Funder name

Public Health Agency for Northern Ireland (UK) - HSC Research and Development Division (ref: EAT/4208/09)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 protocol in http://www.ncbi.nlm.nih.gov/pubmed/23419093

Publication citations

  1. Protocol

    Cross LJ, O'Kane CM, McDowell C, Elborn JJ, Matthay MA, McAuley DF, Keratinocyte growth factor in acute lung injury to reduce pulmonary dysfunction--a randomised placebo-controlled trial (KARE): study protocol., Trials, 2013, 14, 51, doi: 10.1186/1745-6215-14-51.

Additional files

Editorial Notes