KARE - Keratinocyte growth factor in acute lung injury to reduce pulmonary dysfunction

ISRCTN	ISRCTN95690673
DOI	https://doi.org/10.1186/ISRCTN95690673
Clinical Trials Information System (CTIS)	2010-021186-70
Protocol serial number	10089DMCA-CS
Sponsor	Belfast Health and Social Care Trust (UK)
Funder	Public Health Agency for Northern Ireland (UK) - HSC Research and Development Division (ref: EAT/4208/09)

Submission date: 06/09/2010
Registration date: 23/09/2010
Last edited: 22/05/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Danny Francis McAuley
Scientific

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

Study information

Primary study design	Interventional
Study design	Prospective randomised double-blind placebo-controlled phase II multi-centre trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Keratinocyte growth factor in acute lung injury to reduce pulmonary dysfunction: a randomised placebo controlled trial
Study acronym	KARE
Study objectives	The hypothesis is that treatment with palifermin will improve surrogate clinical outcomes in adult patients with acute lung injury and is safe.
Ethics approval(s)	Office for Research Ethics Committees Northern Ireland (ORECNI) HSC REC 2, 04/08/2010, ref: 10/NIR02/32
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Palifermin
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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.
Completion date	31/12/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	60
Key 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.
Key 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
Date of first enrolment	10/09/2010
Date of final enrolment	31/12/2013

Locations

Countries of recruitment

United Kingdom
Northern Ireland

Study participating centre

Royal Victoria Hospital

Belfast
BT12 6BN
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/06/2017		Yes	No
Protocol article	protocol	18/02/2013		Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

22/05/2017: Publication reference added.

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'