Acute Lung Injury
Conditions
Keywords
Acute lung injury, Lung resection
Brief summary
The purpose of this study is to determine whether N-acetylcysteine given intravenously 1 day pre-operatively is effective in preventing inflammation in the lungs, as measured by tests on blood, breath and lung specimens, in patients undergoing surgery to remove a portion of lung.
Detailed description
Acute lung injury occurs following lung resection in about 5% cases, and has a high mortality of around 50%. Management of these patients is largely supportive. Even in patients who do not develop clinical evidence of acute lung injury, markers of inflammation and oxidative stress are present in blood and exhaled breath condensate after lung resection. The purpose of this randomised double-blind placebo-controlled study is to determine whether lung injury can be prevented by pre-administration of N-acetylcysteine.
Interventions
DRUGN-acetylcysteine
N-acetylcysteine 240mg/kg in 1 litre 0.9% saline intravenous over 12 hours pre-operatively
DRUG0.9% saline
0.9% saline 1 litre intravenous over 12 hours pre-operatively
Sponsors
Royal College of Physicians
Royal Brompton & Harefield NHS Foundation Trust
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Elective lung resection for cancer
Exclusion criteria
* Age less than 18 years * Women of child-bearing age or potential * Known allergy to N-acetylcysteine * Oral steroid in the preceding 1 month * N-acetylcysteine in the preceding 1 month * Unable to receive standardised anaesthetic approach
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-operative Plasma IL-6 | Post operative, 24 hours | Plasma IL-6 was measured in duplicate using ELISA. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| N-acetylcysteine Participant received N-acetylcysteine 240mg/kg in 1 litre 0.9% saline intravenous over 12 hours pre-operatively
N-acetylcysteine: N-acetylcysteine 240mg/kg in 1 litre 0.9% saline intravenous over 12 hours pre-operatively | 23 |
| Placebo Participant received 0.9% saline 1 litre intravenous over 12 hours pre-operatively
0.9% saline: 0.9% saline 1 litre intravenous over 12 hours pre-operatively | 24 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | N-acetylcysteine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 68 years STANDARD_DEVIATION 10.1 | 63.9 years STANDARD_DEVIATION 11.5 | 65.95 years STANDARD_DEVIATION 10.8 |
| Duration of one-lung ventilation | 134 minutes STANDARD_DEVIATION 42 | 137 minutes STANDARD_DEVIATION 59 | 135.5 minutes STANDARD_DEVIATION 50.5 |
| FVC | 3.48 litres STANDARD_DEVIATION 1.17 | 3.6 litres STANDARD_DEVIATION 1.01 | 3.54 litres STANDARD_DEVIATION 1.09 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United Kingdom | 23 participants | 24 participants | 47 participants |
| Sex: Female, Male Female | 8 Participants | 9 Participants | 17 Participants |
| Sex: Female, Male Male | 15 Participants | 15 Participants | 30 Participants |
| Spirometry, FEV1 | 2.23 litres STANDARD_DEVIATION 0.97 | 2.56 litres STANDARD_DEVIATION 0.81 | 2.39 litres STANDARD_DEVIATION 0.89 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 24 |
| other Total, other adverse events | 8 / 23 | 5 / 24 |
| serious Total, serious adverse events | 14 / 23 | 12 / 24 |
Outcome results
Primary
Post-operative Plasma IL-6
Plasma IL-6 was measured in duplicate using ELISA.
Time frame: Post operative, 24 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| N-acetylcysteine | Post-operative Plasma IL-6 | 126 pg/ml |
| Placebo | Post-operative Plasma IL-6 | 111 pg/ml |
p-value: 0.09t-test, 2 sided