Respiratory InsufficiencyPhase 2TOESNCT04204967

Totally Transdermal Sedation in the Weaning From Remifentanil Infusion

A Phase 2 study testing Fentanyl Transdermal System and Remifentanil in people with Respiratory Insufficiency and Ventilator Weaning, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.

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

Who is it for?: Ages 18 years and older
Conditions the study is for: Respiratory Insufficiency, Ventilator Weaning, Analgesics, Opioid
What is being tested?: Fentanyl Transdermal System and Remifentanil
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 1 siteItaly
Study dates: 15 Feb 2021to 6 Apr 2024
Phase: Phase 2
Are there results?: None posted in the registry

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

Who may be able to join

Age > 18 yo;
Negative pregnancy test prior to inclusion in the study;
The informed consent form needs to be signed and dated by the patient or a relative/legal guardian before of any procedure related to the study; if the patient is initially unable to sign the informed consent form, but later regains the ability to sign it, a new informed consent form will be given to the patient and must be signed and dated;
Mechanically ventilated in Pressure Support Ventilation, according to the decision to the attending physician;
A patient with prolonged weaning from the mechanical ventilator will be considered eligible. Prolonged weaning is defined as weaning that is still not terminated 7 days after the first separation attempt from the ventilator (by success or death).
Analgesia provided by continuous infusion of remifentanil lasting five days or more and an intolerance to a dose reduction of 0.025 mcg/kg/min defined as the presence of at least one of the following criteria: RASS ≥ 2, a respiratory rate ≥ 35 breaths/minute, a PaCO2 < 30 mmHg, a heart rate > 120 bpm, a systolic blood pressure value > 160 mmHg or an increase of Visual Analogue Scale for pain assessment of ≥ 2 points.

Who cannot join

Hypersensitivity to the active substance or any of the excipients;
Hepatic or renal impairment;
Fever (body temperature ≥ 38 °C) or septic shock, hypothermia (body temperature < 35 °C) or presence of active surface cooling systems;
Hypercapnic patients with a PaCO2 > 45 mmHg;
Current enrollment or plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 30 days or 5 half-lives of the agent, prior to the baseline visit;
Hypoxemic respiratory failure (P/F < 200 mmHg);

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Delirium state defined as RASS ≥ 3 and CAM-ICU positive;
Hemodynamic instability requiring high doses of inotropes or vasopressors;
Any condition that may contraindicate the use of remifentanil or transdermal fentanyl;
Patients with a BMI ≥ 35;
Patient admitted for postoperative monitoring after elective surgery;
EAdi catheter contraindicated.

Trial locations and contacts

1 site in 1 country.

Italy1 site

Fondazione Policlinico Universitario A. Gemelli IRCCS
Roma, 00168

Other trials in Italy

About this study

Official title: Impact of Totally Transdermal Sedation in the Weaning From Remifentanil Infusion Among Critically Ill Patients Undergoing Mechanical Ventilation: a Pilot Randomized-controlled Study (The TOES Trial)

The choice of the sedation protocol has a massive impact on the duration of mechanical ventilation and the timing of extubation. Many sedation protocols are described in the literature. The investigators aim to assess if a transdermal fentanyl-based sedation protocol can have an impact on the global Work of Breathing (WOB)

Read the detailed description

The choice of the sedation protocol has a massive impact on the duration of mechanical ventilation and the timing of extubation. Many sedation protocols are described in the literature. No data are available about the possibility of using transdermal fentanyl as an alternative to intravenous opioids during the weaning phase from mechanical ventilation and the post-extubation period until the discharge from ICU to the ward. The investigators aim to assess if a transdermal fentanyl-based sedation protocol can have an impact on the global Work of Breathing (WOB). Secondary endpoints of the study are the duration of mechanical ventilation, the duration of continuous infusion of opioids, the length of stay in ICU and in hospital. Eligible patients will be randomized in 2 groups: Group 1 will receive remifentanil; Group 2 will receive transdermal fentanyl and remifentanil. An Edi Catheter for diaphragm electrical activity monitoring will be put in place for each patient.

Statistical Analysis: Distribution normality will be assessed with the Kolmogorov-Smirnov test. Continuous variables will be reported expressed as medians (interquartile ranges). Qualitative variables will be reported as frequencies. Analysis on the primary efficacy criterion and other quantitative variables will be assessed with the Wilcoxon-Mann-Whitney test. Categorical outcomes will be compared with the chi-square test, or Fisher's exact test, as appropriate. Cochran-Mantel-Haenszel statistics will be reported for all these results. Two-way analysis of variance (ANOVA) for repeated measures with Bonferroni correction will be used to determine the differences in secondary endpoints. Comparisons between groups regarding these variables at each study time point were performed with the Student's t-test or Mann-Whitney test, as appropriate. Mean difference and 95% confidence interval [Confidence Interval 95%] are reported for most significant results. Two-tail p values≤0.05 Will be considered significant.

Conditions: Respiratory Insufficiency, Ventilator Weaning, Analgesics, Opioid
Being tested: Fentanyl Transdermal System, Remifentanil
Medical subject headings: Respiratory Insufficiency

What participants receive

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

Fentanyl Transdermal SystemDrug
Also called Alghedon
in the experimental arm transdermal fentanyl will be administered with a starting dose of 50 mcg/hr simultaneously with the preexistent remifentanil continue infusion. Remifentanil infusion rate will be increased or decreased based on PaCO2 value resulting from the Arterial Blood Gases sample (ABG) collected at each visit. After randomization, the transdermal fentanyl dose can be modified every 24 hours according to the study protocol to achieve the desired effect in terms of PaCO2 value resulting from the Arterial Blood Gases sample (ABG) collected
RemifentanilDrug
Also called Ultiva
In the active comparator arm remifentanil infusion is administered alone, the infusion rate will be increased or decreased according to the study protocol based on PaCO2 value resulting from the Arterial Blood Gases sample (ABG) collected at each visit.
In the experimental arm remifentanil is use together with transdermal fentanyl

Study groups in NCT04204967
Study group	Role	What they receive
transdermal fentanyl	Experimental	transdermal fentanyl will be administered with a starting dose of 50 mcg/hr simultaneously with the preexistent remifentanil continue infusion. Remifentanil infusion rate will be increased or decreased based on PaCO2 value resulting from the Arterial Blood Gases sample (ABG) collected at each visit. After randomization, the transdermal fentanyl dose can be modified every 24 hours according to the study protocol to achieve the desired effect in terms of PaCO2 value resulting from the Arterial Blood Gases sample (ABG) collected Receives: Drug: Fentanyl Transdermal System; Drug: Remifentanil
IV Remifentanil alone	Active comparator	remifentanil infusion is administered alone, the infusion rate will be increased or decreased according to the study protocol based on PaCO2 value resulting from the Arterial Blood Gases sample (ABG) collected at each visit Receives: Drug: Remifentanil

What is being measured

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

Comparison of the work of breathing (WOB) of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
To demonstrate that the area under the curve (AUC) of the work of breathing per minute (cmH20*sec/min) (assessed at 1, 6, 12, 24 hours for the first day after randomization, and every 24 hours for the following days) in the intervention group is not higher than the control group.
Measured: starts with the randomization and ends 72 hours after randomization
Comparison of the work of breathing per breath of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
cmH20*sec/min
Measured: starts with the randomization and ends 72 hours after randomization
Comparison of the inspiratory effort of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
cmH20
Measured: starts with the randomization and ends 72 hours after randomization
Comparison of the delta electrical activity of the diaphragm (EAdi) of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
microvolt (mcv)
Measured: starts with the randomization and ends 72 hours after randomization
Comparison of the plateau pressures of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
cmH20
Measured: starts with the randomization and ends 72 hours after randomization
Comparison of driving pressures of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
cmH20
Measured: starts with the randomization and ends 72 hours after randomization
Comparison of transpulmonary driving pressures of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
cmH20
Measured: starts with the randomization and ends 72 hours after randomization
Comparison of the pulmonary compliance of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
ml/cmH20
Measured: starts with the randomization and ends 72 hours after randomization
Comparison of P0.1 of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
cmH20
Measured: starts with the randomization and ends 72 hours after randomization
Comparison of P/F ratios of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
The P/F ratio equals the arterial PaO2 (Arterial Oxygen Partial Pressure) (mmHg) divided by the FIO2 (the fraction of inspired oxygen expressed as a decimal)
Measured: starts with the randomization and ends 72 hours after randomization

Secondary outcomes (8)

Comparison of respiratory rates of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
breaths per minute
Measured: starts with the randomization and ends 72 hours after randomization
Comparison of tidal volumes of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
milliliters
Measured: starts with the randomization and ends 72 hours after randomization
Comparison of arterial blood pressure of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
mmHg
Measured: starts with the randomization and ends 72 hours after randomization
Comparison of heart rates of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
bpm
Measured: starts with the randomization and ends 72 hours after randomization
Global duration of mechanical ventilation among the two groups.
Days
Measured: starts with the randomization and ends with the discharge from the intensive care unit.
Global duration of intravenous remifentanil infusion among the two groups.
Hours
Measured: starts with the randomization and ends with the discharge from the intensive care unit.
Length of stay in hospital among the two groups.
Days
Measured: starts with the randomization and ends with the discharge from the Hospital.
Length of stay in ICU among the two groups.
Days
Measured: starts with the randomization and ends with the discharge from the intensive care unit.

Timeline

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

15 Feb 20216 Apr 2024

First posted19 Dec 2019
Study start15 Feb 2021
Primary completion6 Apr 2024
Study completion6 Apr 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (21)Papers the sponsor has linked to this study.
Other trials for Respiratory InsufficiencyStudies of the same condition, open and under way.
More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: 2-arm, single-center, prospective randomized controlled trial.
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04204967
Sponsor's protocol ID: 2687
Other IDs: 2019-002509-22, 2019
Acronym: TOES
Status last verified: Jan 2024
First submitted: 7 Dec 2019
Last updated: 17 May 2024
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Jeong BH, Ko MG, Nam J, Yoo H, Chung CR, Suh GY, Jeon K. Differences in clinical outcomes according to weaning classifications in medical intensive care units. PLoS One. 2015 Apr 15;10(4):e0122810. doi: 10.1371/journal.pone.0122810. eCollection 2015.
PubMed 25876004
Beduneau G, Pham T, Schortgen F, Piquilloud L, Zogheib E, Jonas M, Grelon F, Runge I, Nicolas Terzi, Grange S, Barberet G, Guitard PG, Frat JP, Constan A, Chretien JM, Mancebo J, Mercat A, Richard JM, Brochard L; WIND (Weaning according to a New Definition) Study Group and the REVA (Reseau Europeen de Recherche en Ventilation Artificielle) Network double dagger. Epidemiology of Weaning Outcome according to a New Definition. The WIND Study. Am J Respir Crit Care Med. 2017 Mar 15;195(6):772-783. doi: 10.1164/rccm.201602-0320OC.
PubMed 27626706
Girard TD, Alhazzani W, Kress JP, Ouellette DR, Schmidt GA, Truwit JD, Burns SM, Epstein SK, Esteban A, Fan E, Ferrer M, Fraser GL, Gong MN, Hough CL, Mehta S, Nanchal R, Patel S, Pawlik AJ, Schweickert WD, Sessler CN, Strom T, Wilson KC, Morris PE; ATS/CHEST Ad Hoc Committee on Liberation from Mechanical Ventilation in Adults. An Official American Thoracic Society/American College of Chest Physicians Clinical Practice Guideline: Liberation from Mechanical Ventilation in Critically Ill Adults. Rehabilitation Protocols, Ventilator Liberation Protocols, and Cuff Leak Tests. Am J Respir Crit Care Med. 2017 Jan 1;195(1):120-133. doi: 10.1164/rccm.201610-2075ST.
PubMed 27762595
Penuelas O, Frutos-Vivar F, Fernandez C, Anzueto A, Epstein SK, Apezteguia C, Gonzalez M, Nin N, Raymondos K, Tomicic V, Desmery P, Arabi Y, Pelosi P, Kuiper M, Jibaja M, Matamis D, Ferguson ND, Esteban A; Ventila Group. Characteristics and outcomes of ventilated patients according to time to liberation from mechanical ventilation. Am J Respir Crit Care Med. 2011 Aug 15;184(4):430-7. doi: 10.1164/rccm.201011-1887OC.
PubMed 21616997
Perkins GD, Mistry D, Gates S, Gao F, Snelson C, Hart N, Camporota L, Varley J, Carle C, Paramasivam E, Hoddell B, McAuley DF, Walsh TS, Blackwood B, Rose L, Lamb SE, Petrou S, Young D, Lall R; Breathe Collaborators. Effect of Protocolized Weaning With Early Extubation to Noninvasive Ventilation vs Invasive Weaning on Time to Liberation From Mechanical Ventilation Among Patients With Respiratory Failure: The Breathe Randomized Clinical Trial. JAMA. 2018 Nov 13;320(18):1881-1888. doi: 10.1001/jama.2018.13763.
PubMed 30347090
Muellejans B, Lopez A, Cross MH, Bonome C, Morrison L, Kirkham AJ. Remifentanil versus fentanyl for analgesia based sedation to provide patient comfort in the intensive care unit: a randomized, double-blind controlled trial [ISRCTN43755713]. Crit Care. 2004 Feb;8(1):R1-R11. doi: 10.1186/cc2398. Epub 2003 Nov 20.
PubMed 14975049
Akinci SB, Kanbak M, Guler A, Aypar U. Remifentanil versus fentanyl for short-term analgesia-based sedation in mechanically ventilated postoperative children. Paediatr Anaesth. 2005 Oct;15(10):870-8. doi: 10.1111/j.1460-9592.2005.01574.x.
PubMed 16176316
Zhu Y, Wang Y, Du B, Xi X. Could remifentanil reduce duration of mechanical ventilation in comparison with other opioids for mechanically ventilated patients? A systematic review and meta-analysis. Crit Care. 2017 Aug 3;21(1):206. doi: 10.1186/s13054-017-1789-8.
PubMed 28774327
Futier E, Chanques G, Cayot Constantin S, Vernis L, Barres A, Guerin R, Chartier C, Perbet S, Petit A, Jabaudon M, Bazin JE, Constantin JM. Influence of opioid choice on mechanical ventilation duration and ICU length of stay. Minerva Anestesiol. 2012 Jan;78(1):46-53. Epub 2011 Nov 5.
PubMed 21971434
Natalini G, Di Maio A, Rosano A, Ferretti P, Bertelli M, Bernardini A. Remifentanil improves breathing pattern and reduces inspiratory workload in tachypneic patients. Respir Care. 2011 Jun;56(6):827-33. doi: 10.4187/respcare.01014. Epub 2011 Feb 11.
PubMed 21333087
Newshan G. Heat-related toxicity with the fentanyl transdermal patch. J Pain Symptom Manage. 1998 Nov;16(5):277-8. doi: 10.1016/s0885-3924(98)00100-6. No abstract available.
PubMed 9846020
Carter KA. Heat-associated increase in transdermal fentanyl absorption. Am J Health Syst Pharm. 2003 Jan 15;60(2):191-2. doi: 10.1093/ajhp/60.2.191. No abstract available.
PubMed 12561665
Lotsch J, Walter C, Parnham MJ, Oertel BG, Geisslinger G. Pharmacokinetics of non-intravenous formulations of fentanyl. Clin Pharmacokinet. 2013 Jan;52(1):23-36. doi: 10.1007/s40262-012-0016-7.
PubMed 23100195
Bulow HH, Linnemann M, Berg H, Lang-Jensen T, LaCour S, Jonsson T. Respiratory changes during treatment of postoperative pain with high dose transdermal fentanyl. Acta Anaesthesiol Scand. 1995 Aug;39(6):835-9. doi: 10.1111/j.1399-6576.1995.tb04180.x.
PubMed 7484044
Beck J, Gottfried SB, Navalesi P, Skrobik Y, Comtois N, Rossini M, Sinderby C. Electrical activity of the diaphragm during pressure support ventilation in acute respiratory failure. Am J Respir Crit Care Med. 2001 Aug 1;164(3):419-24. doi: 10.1164/ajrccm.164.3.2009018.
PubMed 11500343

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 17 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Impact of Totally Transdermal Sedation in the Weaning From Remifentanil Infusion Among Critically Ill Patients Undergoing Mechanical Ventilation: a Pilot Randomized-controlled Study (The TOES Trial)
ClinicalTrials.gov ID: NCT04204967
Acronym / sponsor ID: TOES / 2687
Conditions: Respiratory Insufficiency, Ventilator Weaning, Analgesics, Opioid
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
Study start: 15 Feb 2021 (actual)
Primary completion: 6 Apr 2024 (actual)
Study completion: 6 Apr 2024 (actual)
First posted: 19 Dec 2019 (actual)
Results: Not posted in the source record

Clinical summary

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

The choice of the sedation protocol has a massive impact on the duration of mechanical ventilation and the timing of extubation. Many sedation protocols are described in the literature. The investigators aim to assess if a transdermal fentanyl-based sedation protocol can have an impact on the global Work of Breathing (WOB)

Detailed description

The choice of the sedation protocol has a massive impact on the duration of mechanical ventilation and the timing of extubation. Many sedation protocols are described in the literature. No data are available about the possibility of using transdermal fentanyl as an alternative to intravenous opioids during the weaning phase from mechanical ventilation and the post-extubation period until the discharge from ICU to the ward. The investigators aim to assess if a transdermal fentanyl-based sedation protocol can have an impact on the global Work of Breathing (WOB). Secondary endpoints of the study are the duration of mechanical ventilation, the duration of continuous infusion of opioids, the length of stay in ICU and in hospital. Eligible patients will be randomized in 2 groups: Group 1 will receive remifentanil; Group 2 will receive transdermal fentanyl and remifentanil. An Edi Catheter for diaphragm electrical activity monitoring will be put in place for each patient.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: 2-arm, single-center, prospective randomized controlled trial.

Arm	Type	Receives
transdermal fentanyl	Experimental	Drug: Fentanyl Transdermal System, Drug: Remifentaniltransdermal fentanyl will be administered with a starting dose of 50 mcg/hr simultaneously with the preexistent remifentanil continue infusion. Remifentanil infusion rate will be increased or decreased based on PaCO2 value resulting from the Arterial Blood Gases sample (ABG) collected at each visit. After randomization, the transdermal fentanyl dose can be modified every 24 hours according to the study protocol to achieve the desired effect in terms of PaCO2 value resulting from the Arterial Blood Gases sample (ABG) collected
IV Remifentanil alone	Active comparator	Drug: Remifentanilremifentanil infusion is administered alone, the infusion rate will be increased or decreased according to the study protocol based on PaCO2 value resulting from the Arterial Blood Gases sample (ABG) collected at each visit

Who may qualify

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

Key inclusion criteria (6 listed)

Age > 18 yo;
Negative pregnancy test prior to inclusion in the study;
The informed consent form needs to be signed and dated by the patient or a relative/legal guardian before of any procedure related to the study; if the patient is initially unable to sign the informed consent form, but later regains the ability to sign it, a new informed consent form will be given to the patient and must be signed and dated;
Mechanically ventilated in Pressure Support Ventilation, according to the decision to the attending physician;
A patient with prolonged weaning from the mechanical ventilator will be considered eligible. Prolonged weaning is defined as weaning that is still not terminated 7 days after the first separation attempt from the ventilator (by success or death).

Key exclusion criteria (12 listed)

Hypersensitivity to the active substance or any of the excipients;
Hepatic or renal impairment;
Fever (body temperature ≥ 38 °C) or septic shock, hypothermia (body temperature < 35 °C) or presence of active surface cooling systems;
Hypercapnic patients with a PaCO2 > 45 mmHg;
Current enrollment or plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 30 days or 5 half-lives of the agent, prior to the baseline visit;

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
Fentanyl Transdermal SystemAlso: Alghedonin the experimental arm transdermal fentanyl will be administered with a starting dose of 50 mcg/hr simultaneously with the preexistent remifentanil continue infusion. Remifentanil infusion rate will be increased or decreased based on PaCO2 value resulting from the Arterial Blood Gases sample (ABG) collected at each visit. After randomization, the transdermal fentanyl dose can be modified every 24 hours according to the study protocol to achieve the desired effect in terms of PaCO2 value resulting from the Arterial Blood Gases sample (ABG) collected	Drug	transdermal fentanyl
RemifentanilAlso: UltivaIn the active comparator arm remifentanil infusion is administered alone, the infusion rate will be increased or decreased according to the study protocol based on PaCO2 value resulting from the Arterial Blood Gases sample (ABG) collected at each visit. In the experimental arm remifentanil is use together with transdermal fentanyl	Drug	IV Remifentanil alone, transdermal fentanyl

Primary outcome

Comparison of the work of breathing (WOB) of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
Time frame: starts with the randomization and ends 72 hours after randomization
To demonstrate that the area under the curve (AUC) of the work of breathing per minute (cmH20*sec/min) (assessed at 1, 6, 12, 24 hours for the first day after randomization, and every 24 hours for the following days) in the intervention group is not higher than the control group.
Comparison of the work of breathing per breath of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
Time frame: starts with the randomization and ends 72 hours after randomization
cmH20*sec/min
Comparison of the inspiratory effort of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
Time frame: starts with the randomization and ends 72 hours after randomization
cmH20
Comparison of the delta electrical activity of the diaphragm (EAdi) of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
Time frame: starts with the randomization and ends 72 hours after randomization
microvolt (mcv)
Comparison of the plateau pressures of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
Time frame: starts with the randomization and ends 72 hours after randomization
cmH20
Comparison of driving pressures of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
Time frame: starts with the randomization and ends 72 hours after randomization
cmH20
Comparison of transpulmonary driving pressures of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
Time frame: starts with the randomization and ends 72 hours after randomization
cmH20
Comparison of the pulmonary compliance of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
Time frame: starts with the randomization and ends 72 hours after randomization
ml/cmH20
Comparison of P0.1 of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
Time frame: starts with the randomization and ends 72 hours after randomization
cmH20
Comparison of P/F ratios of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
Time frame: starts with the randomization and ends 72 hours after randomization
The P/F ratio equals the arterial PaO2 (Arterial Oxygen Partial Pressure) (mmHg) divided by the FIO2 (the fraction of inspired oxygen expressed as a decimal)

8 secondary outcomes

Comparison of respiratory rates of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
Time frame: starts with the randomization and ends 72 hours after randomization
Comparison of tidal volumes of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
Time frame: starts with the randomization and ends 72 hours after randomization
Comparison of arterial blood pressure of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
Time frame: starts with the randomization and ends 72 hours after randomization
Comparison of heart rates of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
Time frame: starts with the randomization and ends 72 hours after randomization
Global duration of mechanical ventilation among the two groups.
Time frame: starts with the randomization and ends with the discharge from the intensive care unit.
Global duration of intravenous remifentanil infusion among the two groups.
Time frame: starts with the randomization and ends with the discharge from the intensive care unit.
Length of stay in hospital among the two groups.
Time frame: starts with the randomization and ends with the discharge from the Hospital.
Length of stay in ICU among the two groups.
Time frame: starts with the randomization and ends with the discharge from the intensive care unit.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2024.
Background: PubMed 25876004Jeong BH, Ko MG, Nam J, Yoo H, Chung CR, Suh GY, Jeon K. Differences in clinical outcomes according to weaning classifications in medical intensive care units. PLoS One. 2015 Apr 15;10(4):e0122810. doi: 10.1371/journal.pone.0122810. eCollection 2015.
Background: PubMed 27626706Beduneau G, Pham T, Schortgen F, Piquilloud L, Zogheib E, Jonas M, Grelon F, Runge I, Nicolas Terzi, Grange S, Barberet G, Guitard PG, Frat JP, Constan A, Chretien JM, Mancebo J, Mercat A, Richard JM, Brochard L; WIND (Weaning according to a New Definition) Study Group and the REVA (Reseau Europeen de Recherche en Ventilation Artificielle) Network double dagger. Epidemiology of Weaning Outcome according to a New Definition. The WIND Study. Am J Respir Crit Care Med. 2017 Mar 15;195(6):772-783. doi: 10.1164/rccm.201602-0320OC.
Background: PubMed 27762595Girard TD, Alhazzani W, Kress JP, Ouellette DR, Schmidt GA, Truwit JD, Burns SM, Epstein SK, Esteban A, Fan E, Ferrer M, Fraser GL, Gong MN, Hough CL, Mehta S, Nanchal R, Patel S, Pawlik AJ, Schweickert WD, Sessler CN, Strom T, Wilson KC, Morris PE; ATS/CHEST Ad Hoc Committee on Liberation from Mechanical Ventilation in Adults. An Official American Thoracic Society/American College of Chest Physicians Clinical Practice Guideline: Liberation from Mechanical Ventilation in Critically Ill Adults. Rehabilitation Protocols, Ventilator Liberation Protocols, and Cuff Leak Tests. Am J Respir Crit Care Med. 2017 Jan 1;195(1):120-133. doi: 10.1164/rccm.201610-2075ST.
Background: PubMed 21616997Penuelas O, Frutos-Vivar F, Fernandez C, Anzueto A, Epstein SK, Apezteguia C, Gonzalez M, Nin N, Raymondos K, Tomicic V, Desmery P, Arabi Y, Pelosi P, Kuiper M, Jibaja M, Matamis D, Ferguson ND, Esteban A; Ventila Group. Characteristics and outcomes of ventilated patients according to time to liberation from mechanical ventilation. Am J Respir Crit Care Med. 2011 Aug 15;184(4):430-7. doi: 10.1164/rccm.201011-1887OC.
Background: PubMed 30347090Perkins GD, Mistry D, Gates S, Gao F, Snelson C, Hart N, Camporota L, Varley J, Carle C, Paramasivam E, Hoddell B, McAuley DF, Walsh TS, Blackwood B, Rose L, Lamb SE, Petrou S, Young D, Lall R; Breathe Collaborators. Effect of Protocolized Weaning With Early Extubation to Noninvasive Ventilation vs Invasive Weaning on Time to Liberation From Mechanical Ventilation Among Patients With Respiratory Failure: The Breathe Randomized Clinical Trial. JAMA. 2018 Nov 13;320(18):1881-1888. doi: 10.1001/jama.2018.13763.
Background: PubMed 14975049Muellejans B, Lopez A, Cross MH, Bonome C, Morrison L, Kirkham AJ. Remifentanil versus fentanyl for analgesia based sedation to provide patient comfort in the intensive care unit: a randomized, double-blind controlled trial [ISRCTN43755713]. Crit Care. 2004 Feb;8(1):R1-R11. doi: 10.1186/cc2398. Epub 2003 Nov 20.
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Individual participant dataSharing planned: No

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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.

Prof. A Caricato, MD principal investigator

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

1 site 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?

The sponsor lists 6 inclusion and 12 exclusion criteria. 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 17 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Comparison of the work of breathing (WOB) of the patients randomized to receive transdermal fentanyl vs. remifentanil alone. (time frame: starts with the randomization and ends 72 hours after randomization). The study lists 10 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 NCT04204967, which also lists 21 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 17 May 2024.