Delirium, Nicotine Replacement Therapy, Psychomotor Agitation, Substance Withdrawal Syndrome
Conditions
Keywords
Delirium, Psychomotor Agitation, Substance Withdrawal Syndrome, Nicotine replacement therapy
Brief summary
The purpose of this study is to determine whether transdermal nicotine replacement therapy is safe and effective for treating nicotine withdrawal symptoms in the critically ill smoking patient.
Detailed description
Cigarette smoking remains the leading cause of preventable disease and premature death worldwide. There are about 1.2 billion smokers in the world, half of whom will die from diseases caused by smoking. Smoking causes 5 million deaths per year, and if present trends continue, 10 million smokers per year are projected to die by 2025. Furthermore, abstinence from the highly addictive tobacco products can lead to withdrawal symptoms. Although these symptoms are non-life threatening in healthy and hospitalized adults they are not well described in the mechanically ventilated active smoking patient. Retrospective studies found a higher, lower or equal mortality in critically ill patients receiving nicotine replacement therapy compared to patients receiving no nicotine replacement. Because of these conflicting results and the absence of a randomized controlled trial studying the efficacy and safety of transdermal nicotine replacement therapy in the critically ill smoking patient a clinical study will be conducted.
Interventions
DRUGTransdermal nicotine patch
The test product is a transdermal nicotine patch. The dosage of the test product depends on the amount of cigarettes used by a specific patient (21 or more or less than 21) delivering 21 or 14 mg nicotine/24 hrs. During the study period of thirty (30) days a patch will be applicated daily.
OTHERCutaneous patch, containing no active substances
During the study period of thirty (30) days, the control product will be applicated daily.
Sponsors
Deventer Ziekenhuis
Wageningen University
Gelderse Vallei Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Any patient admitted to the intensive care unit must meet all of the following criteria to be eligible for the study: * Critically ill active smoking patient * Being mechanically ventilated * Start of study product application within 48 hours after ICU admission * Expected to be mechanically ventilated for more than 48 hours after start of application of the study product
Exclusion criteria
Any patient admitted to the intensive care unit meeting one or more of the following criteria is not eligible for the study: * Patient younger than 18 years * Patient or next of kin denying research authorization * Pregnancy * Breastfeeding women * History of chronic dementia or psychosis * (Acute) neurologic disease on admission, possibly confounding study objectives (TBI, stroke, ICH/SAH, seizures, meningitis, encephalitis, intracranial tumor) * Patient receiving any form of NRT within two weeks before admission * Patient not understanding Dutch * Patient with acute myocardial infarction * Patient with severe cardiac arrhythmia * Patient with unstable or deteriorating angina pectoris * Patient with generalized acute or chronic skin diseases interfering with NRT absorption * Patient with severe hearing deficiency * Moribund patient * Patient with known hypersensibility to nicotine or components of the transdermal therapeutic system * Patient with known hypersensibility to patches * Patient participating in an other study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 30-day Mortality | 30 days | — |
| Patient Location Day 30 | On day 30 | In the ICU or hospital at day 30 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 90-day Mortality | Day 90 followup | Mortality at day 90 after enrollment |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nicotine Patch Transdermal nicotine patch: The test product is a transdermal nicotine patch. The dosage of the test product depends on the amount of cigarettes used by a specific patient (21 or more or less than 21) delivering 21 or 14 mg nicotine/24 hrs. During the study period of thirty (30) days a patch will be applied daily. | 21 |
| Control Patch The control product is a look-alike cutaneous patch comparable to the test product, containing no nicotine or other active substances. During the study period of thirty (30) days, the control product will be applied daily. | 26 |
| Total | 47 |
Baseline characteristics
| Characteristic | Nicotine Patch | Control Patch | Total |
|---|---|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 10.55 | 65.2 years STANDARD_DEVIATION 9.13 | 62.9 years STANDARD_DEVIATION 10 |
| Region of Enrollment Netherlands | 21 participants | 26 participants | 47 participants |
| Sex: Female, Male Female | 9 Participants | 10 Participants | 19 Participants |
| Sex: Female, Male Male | 12 Participants | 16 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 21 | 2 / 26 |
| other Total, other adverse events | 21 / 21 | 26 / 26 |
| serious Total, serious adverse events | 4 / 21 | 11 / 26 |
Outcome results
Primary
30-day Mortality
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Replacement | 30-day Mortality | 9.5 percentage of patients |
| Control | 30-day Mortality | 7.7 percentage of patients |
Primary
Patient Location Day 30
In the ICU or hospital at day 30
Time frame: On day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nicotine Replacement | Patient Location Day 30 | 1 Participants |
| Control | Patient Location Day 30 | 11 Participants |
Secondary
90-day Mortality
Mortality at day 90 after enrollment
Time frame: Day 90 followup
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Replacement | 90-day Mortality | 14.3 percentage of patients |
| Control | 90-day Mortality | 19.2 percentage of patients |
Post Hoc
Time in Normal Brain Function D10
Time alive without delirium and without sedation or coma
Time frame: 10 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nicotine Replacement | Time in Normal Brain Function D10 | 160 hours |
| Control | Time in Normal Brain Function D10 | 88 hours |
Post Hoc
Time in Normal Brain Function D20
Time spent alive without delirium and without sedation or coma
Time frame: 20 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nicotine Replacement | Time in Normal Brain Function D20 | 400 hours |
| Control | Time in Normal Brain Function D20 | 304 hours |