KARE - Keratinocyte growth factor in acute lung injury to reduce pulmonary dysfunction
| ISRCTN | ISRCTN95690673 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN95690673 |
| EudraCT/CTIS number | 2010-021186-70 |
| Secondary identifying numbers | 10089DMCA-CS |
- 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
Not provided at time of registration
Contact information
Prof Danny Francis McAuley
Scientific
Scientific
Microbiology Building
Royal Victoria Hospital
Grosvenor Road
Belfast
BT12 6BN
United Kingdom
Study information
| Study design | Prospective randomised double-blind placebo-controlled phase II multi-centre trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Keratinocyte growth factor in acute lung injury to reduce pulmonary dysfunction: a randomised placebo controlled trial |
| Study 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. |
| Ethics approval(s) | Office for Research Ethics Committees Northern Ireland (ORECNI) HSC REC 2, 04/08/2010, ref: 10/NIR02/32 |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Palifermin |
| Primary outcome measure | 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 study start date | 10/09/2010 |
| Overall study end date | 31/12/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 60 |
| 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 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
- Northern Ireland
- United Kingdom
Study participating centre
Royal Victoria Hospital
Belfast
BT12 6BN
United Kingdom
BT12 6BN
United Kingdom
Sponsor information
Belfast Health and Social Care Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
c/o Professor Ian Young
Trust Research Office
2nd Floor King Edward Building
Royal Victoria Hospitals
Grosvenor Road
Belfast
BT12 6BA
Northern Ireland
United Kingdom
| Website | http://www.belfasttrust.hscni.net/ |
|---|---|
"ROR" |
https://ror.org/02tdmfk69 |
Funders
Funder type
Government
Public Health Agency for Northern Ireland (UK) - HSC Research and Development Division (ref: EAT/4208/09)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 18/02/2013 | Yes | No | |
| Results article | results | 01/06/2017 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
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'
