DeliriumPhase 4NicGoWellNCT01362959

Nicotine Replacement Therapy in the Intensive Care Unit

A Phase 4 study testing Transdermal nicotine patch and Cutaneous patch, containing no active substances in people with Delirium and Psychomotor Agitation, run by Gelderse Vallei Hospital at 2 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Delirium, Psychomotor Agitation, Substance Withdrawal Syndrome
What is being tested?: Transdermal nicotine patch and Cutaneous patch, containing no active substances
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 47 participants
Where: 2 sitesNetherlands
Study dates: Jun 2012to Aug 2016
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

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

Trial locations and contacts

2 sites in 1 country.

Netherlands2 sites

Deventer Hospital
Deventer, Overijssel, 7416 SE
Gelderse Vallei Hospital
Ede, Gelderland, 6716 RP

Other trials in Netherlands

About this study

Official title: Nicotine Replacement Therapy in the Intensive Care Unit: a Randomized, Controlled Pilot Study

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.

Read the 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.

Conditions: Delirium, Psychomotor Agitation, Substance Withdrawal Syndrome, Nicotine Replacement Therapy
Being tested: Transdermal nicotine patch, Cutaneous patch, containing no active substances
Keywords: Delirium, Psychomotor Agitation, Substance Withdrawal Syndrome, Nicotine replacement therapy
Medical subject headings: Delirium, Psychomotor Agitation, Substance Withdrawal Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Transdermal nicotine patchDrug
Also called Nicotinell patch, regulated delivery 35 mg. RVG 14830, Nicotinell patch, regulated delivery 52.5 mg. RVG 14831
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.
Cutaneous patch, containing no active substancesOther
During the study period of thirty (30) days, the control product will be applicated daily.

Study groups in NCT01362959
Study group	Role	What they receive
Nicotine patch	Experimental	Not described Receives: Drug: Transdermal nicotine patch
Control patch	Placebo comparator	The control product is a look-alike patch compared to the test product, containing no nicotine or other active substances. Receives: Other: Cutaneous patch, containing no active substances

What is being measured

The primary outcome is the main question the study is designed to answer.

30-day Mortality
Measured: 30 days
Patient Location Day 30
In the ICU or hospital at day 30
Measured: On day 30

Secondary outcomes (1)

90-day Mortality
Mortality at day 90 after enrollment
Measured: Day 90 followup

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2012Aug 2016

First posted1 Jun 2011 (estimated)
Study startJun 2012
Primary completionAug 2016
Study completionAug 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (16)Papers the sponsor has linked to this study.
Other trials for DeliriumStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 47 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01362959
Sponsor's protocol ID: NicGoWell1.0
Other IDs: 2011-002458-29
Acronym: NicGoWell
Status last verified: Mar 2018
First submitted: 26 May 2011
Last updated: 10 Oct 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Hays JT, Ebbert JO. Adverse effects and tolerability of medications for the treatment of tobacco use and dependence. Drugs. 2010 Dec 24;70(18):2357-72. doi: 10.2165/11538190-000000000-00000.
PubMed 21142259
Moss M, Burnham EL. Alcohol abuse in the critically ill patient. Lancet. 2006 Dec 23;368(9554):2231-42. doi: 10.1016/S0140-6736(06)69490-7.
PubMed 17189035
Benowitz NL. Nicotine addiction. N Engl J Med. 2010 Jun 17;362(24):2295-303. doi: 10.1056/NEJMra0809890. No abstract available.
PubMed 20554984
Hatsukami DK, Stead LF, Gupta PC. Tobacco addiction. Lancet. 2008 Jun 14;371(9629):2027-38. doi: 10.1016/S0140-6736(08)60871-5.
PubMed 18555914
Mills EJ, Wu P, Lockhart I, Wilson K, Ebbert JO. Adverse events associated with nicotine replacement therapy (NRT) for smoking cessation. A systematic review and meta-analysis of one hundred and twenty studies involving 177,390 individuals. Tob Induc Dis. 2010 Jul 13;8(1):8. doi: 10.1186/1617-9625-8-8.
PubMed 20626883
Lucidarme O, Seguin A, Daubin C, Ramakers M, Terzi N, Beck P, Charbonneau P, du Cheyron D. Nicotine withdrawal and agitation in ventilated critically ill patients. Crit Care. 2010;14(2):R58. doi: 10.1186/cc8954. Epub 2010 Apr 9.
PubMed 20380688
Mayer SA, Chong JY, Ridgway E, Min KC, Commichau C, Bernardini GL. Delirium from nicotine withdrawal in neuro-ICU patients. Neurology. 2001 Aug 14;57(3):551-3. doi: 10.1212/wnl.57.3.551.
PubMed 11502936
Moreno R, Vincent JL, Matos R, Mendonca A, Cantraine F, Thijs L, Takala J, Sprung C, Antonelli M, Bruining H, Willatts S. The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis related Problems of the ESICM. Intensive Care Med. 1999 Jul;25(7):686-96. doi: 10.1007/s001340050931.
PubMed 10470572
Lee AH, Afessa B. The association of nicotine replacement therapy with mortality in a medical intensive care unit. Crit Care Med. 2007 Jun;35(6):1517-21. doi: 10.1097/01.CCM.0000266537.86437.38.
PubMed 17452926
Paciullo CA, Short MR, Steinke DT, Jennings HR. Impact of nicotine replacement therapy on postoperative mortality following coronary artery bypass graft surgery. Ann Pharmacother. 2009 Jul;43(7):1197-202. doi: 10.1345/aph.1L423. Epub 2009 Jun 30.
PubMed 19567657
Seder DB, Schmidt JM, Badjatia N, Fernandez L, Rincon F, Claassen J, Gordon E, Carrera E, Kurtz P, Lee K, Connolly ES, Mayer SA. Transdermal nicotine replacement therapy in cigarette smokers with acute subarachnoid hemorrhage. Neurocrit Care. 2011 Feb;14(1):77-83. doi: 10.1007/s12028-010-9456-9.
PubMed 20949331
Cartin-Ceba R, Warner DO, Hays JT, Afessa B. Nicotine replacement therapy in critically ill patients: a prospective observational cohort study. Crit Care Med. 2011 Jul;39(7):1635-40. doi: 10.1097/CCM.0b013e31821867b8.
PubMed 21494111
Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008 Jun;36(5):309-32. doi: 10.1016/j.ajic.2008.03.002. No abstract available.
PubMed 18538699
Centers for Disease Control and Prevention (CDC). Vital signs: central line-associated blood stream infections--United States, 2001, 2008, and 2009. MMWR Morb Mortal Wkly Rep. 2011 Mar 4;60(8):243-8.
PubMed 21368740
Hsieh SJ, Ware LB, Eisner MD, Yu L, Jacob P 3rd, Havel C, Goniewicz ML, Matthay MA, Benowitz NL, Calfee CS. Biomarkers increase detection of active smoking and secondhand smoke exposure in critically ill patients. Crit Care Med. 2011 Jan;39(1):40-5. doi: 10.1097/CCM.0b013e3181fa4196.
PubMed 20935560

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 10 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Nicotine Replacement Therapy in the Intensive Care Unit: a Randomized, Controlled Pilot Study
ClinicalTrials.gov ID: NCT01362959
Acronym / sponsor ID: NicGoWell / NicGoWell1.0
Conditions: Delirium, Psychomotor Agitation, Substance Withdrawal Syndrome, Nicotine Replacement Therapy
Keywords: Delirium, Psychomotor Agitation, Substance Withdrawal Syndrome, Nicotine replacement therapy
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 47 participants (actual)
Lead sponsor: Gelderse Vallei HospitalUniversity, hospital or other
Collaborators: Deventer Ziekenhuis, Wageningen University
Study start: Jun 2012
Primary completion: Aug 2016 (actual)
Study completion: Aug 2016 (actual)
First posted: 1 Jun 2011 (estimated)
Results: Posted 10 Oct 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Retrospective studies found a higher, lower or equal mortality in critically ill patients receiving nicotine replacement therapy compared to patients receiving no nicotine replacement.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Nicotine patch	Experimental	Drug: Transdermal nicotine patch
Control patch	Placebo comparator	Other: Cutaneous patch, containing no active substancesThe control product is a look-alike patch compared to the test product, containing no nicotine or other active substances.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Transdermal nicotine patchAlso: Nicotinell patch, regulated delivery 35 mg. RVG 14830, Nicotinell patch, regulated delivery 52.5 mg. RVG 14831The 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.	Drug	Nicotine patch
Cutaneous patch, containing no active substancesDuring the study period of thirty (30) days, the control product will be applicated daily.	Other	Control patch

Primary outcome

30-day Mortality
Time frame: 30 days
Patient Location Day 30
Time frame: On day 30
In the ICU or hospital at day 30

1 secondary outcome

90-day Mortality
Time frame: Day 90 followup

Results and safety

Results posted to the registry on 10 Oct 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Nicotine Patch	21	21
Control Patch	26	26

Primary outcome: 30-day Mortality

Time frame: 30 days. Number. Unit: percentage of patients

Measure	Nicotine Replacement n = 21	Control n = 26
Value	9.5	7.7

Primary outcome: Patient Location Day 30

Time frame: On day 30. Count of participants. Unit: Participants

Measure	Nicotine Replacement n = 21	Control n = 26
Value	1	11

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 30 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Nicotine Replacement	4 of 21 (19%)	21 of 21 (100%)	2 of 21
Control	11 of 26 (42.3%)	26 of 26 (100%)	2 of 26

Limitations and caveats (from the sponsor): Pilot study, therefore small numbers

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 21142259Hays JT, Ebbert JO. Adverse effects and tolerability of medications for the treatment of tobacco use and dependence. Drugs. 2010 Dec 24;70(18):2357-72. doi: 10.2165/11538190-000000000-00000.
Background: PubMed 17189035Moss M, Burnham EL. Alcohol abuse in the critically ill patient. Lancet. 2006 Dec 23;368(9554):2231-42. doi: 10.1016/S0140-6736(06)69490-7.
Background: PubMed 20554984Benowitz NL. Nicotine addiction. N Engl J Med. 2010 Jun 17;362(24):2295-303. doi: 10.1056/NEJMra0809890. No abstract available.
Background: PubMed 18555914Hatsukami DK, Stead LF, Gupta PC. Tobacco addiction. Lancet. 2008 Jun 14;371(9629):2027-38. doi: 10.1016/S0140-6736(08)60871-5.
Background: PubMed 20626883Mills EJ, Wu P, Lockhart I, Wilson K, Ebbert JO. Adverse events associated with nicotine replacement therapy (NRT) for smoking cessation. A systematic review and meta-analysis of one hundred and twenty studies involving 177,390 individuals. Tob Induc Dis. 2010 Jul 13;8(1):8. doi: 10.1186/1617-9625-8-8.
Background: PubMed 20380688Lucidarme O, Seguin A, Daubin C, Ramakers M, Terzi N, Beck P, Charbonneau P, du Cheyron D. Nicotine withdrawal and agitation in ventilated critically ill patients. Crit Care. 2010;14(2):R58. doi: 10.1186/cc8954. Epub 2010 Apr 9.
Background: PubMed 11502936Mayer SA, Chong JY, Ridgway E, Min KC, Commichau C, Bernardini GL. Delirium from nicotine withdrawal in neuro-ICU patients. Neurology. 2001 Aug 14;57(3):551-3. doi: 10.1212/wnl.57.3.551.
Background: PubMed 10470572Moreno R, Vincent JL, Matos R, Mendonca A, Cantraine F, Thijs L, Takala J, Sprung C, Antonelli M, Bruining H, Willatts S. The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis related Problems of the ESICM. Intensive Care Med. 1999 Jul;25(7):686-96. doi: 10.1007/s001340050931.
Background: PubMed 17452926Lee AH, Afessa B. The association of nicotine replacement therapy with mortality in a medical intensive care unit. Crit Care Med. 2007 Jun;35(6):1517-21. doi: 10.1097/01.CCM.0000266537.86437.38.
Background: PubMed 19567657Paciullo CA, Short MR, Steinke DT, Jennings HR. Impact of nicotine replacement therapy on postoperative mortality following coronary artery bypass graft surgery. Ann Pharmacother. 2009 Jul;43(7):1197-202. doi: 10.1345/aph.1L423. Epub 2009 Jun 30.
Background: PubMed 20949331Seder DB, Schmidt JM, Badjatia N, Fernandez L, Rincon F, Claassen J, Gordon E, Carrera E, Kurtz P, Lee K, Connolly ES, Mayer SA. Transdermal nicotine replacement therapy in cigarette smokers with acute subarachnoid hemorrhage. Neurocrit Care. 2011 Feb;14(1):77-83. doi: 10.1007/s12028-010-9456-9.
Background: PubMed 21494111Cartin-Ceba R, Warner DO, Hays JT, Afessa B. Nicotine replacement therapy in critically ill patients: a prospective observational cohort study. Crit Care Med. 2011 Jul;39(7):1635-40. doi: 10.1097/CCM.0b013e31821867b8.
Website Gelderse Vallei HospitalLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ben Jong,de, MD principal investigator

Gelderse Vallei Hospital

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

30-day Mortality (time frame: 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01362959, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2018.