Clinical trial
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)
Name
2687
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. The investigators aim to assess if a transdermal fentanyl-based sedation protocol can have an impact on the global Work of Breathing (WOB)
Trial arms
Trial start
2021-02-15
Estimated PCD
2024-04-06
Trial end
2024-04-06
Status
Completed
Phase
Early phase I
Treatment
Fentanyl Transdermal System
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
Arms:
transdermal fentanyl
Other names:
Alghedon
Remifentanil
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
Arms:
IV Remifentanil alone, transdermal fentanyl
Other names:
Ultiva
Size
24
Primary endpoint
Comparison of the work of breathing (WOB) of the patients randomized to receive transdermal fentanyl vs. remifentanil alone.
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.
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.
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.
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.
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.
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.
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.
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.
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.
starts with the randomization and ends 72 hours after randomization
Eligibility criteria
Inclusion Criteria:
* 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.
Exclusion Criteria:
* 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);
* 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.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '2-arm, single-center, prospective randomized controlled trial.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 24, 'type': 'ACTUAL'}}
Updated at
2024-05-17
1 organization
2 products
4 indications
Product
FentanylIndication
Respiratory InsufficiencyIndication
ventilator weaningIndication
AnalgesicsIndication
OpioidProduct
Remifentanil