Fentanyl Versus Hydromorphone in Patients on Mechanical Ventilation

NCT ID: NCT07224620

Last Updated: 2025-11-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-30
• Study Completion Date: 2026-06-30

Brief Summary

Patients with respiratory failure who require mechanical ventilation are not only at risk of death, but also of complications of prolonged ICU stay. Patients may have significant functional decline, impact in quality of life, develop psychiatric disorders and at long-term can lead to significant cost to society. Although sedation and analgesia are considered only supportive therapy, several studies have shown that in patients on mechanical ventilation, different approaches can have significant impact on patient centered outcomes. However, to date, randomized clinical trials on critically ill patients have mostly evaluated the sedative agent but not the analgesic agent. Although morphine and its derivates are the most common used opioid analgesic agents in the critical care setting, only some retrospective studies and some prospective studies compared them head-to-head (ramifentanyl versus morphine and fentanyl versus morphine). Current guidelines recommend choosing the analgesic agent based on pharmacokinectics, physician experience and side-effects profile. To evaluate the differences of two standard-of-care analgosedation agents, the FenHydro trial will be a cluster randomized, pragmatic, pilot and feasibility superiority clinical trial in mechanically ventilated patients in the ICU. The main question the study hopes to answer is whether there is any difference in morphine milligram equivalents administered during mechanical ventilation.

Detailed Description

Fentanyl is a synthetic derivate of morphine that is 100 times more potent than morphine, has a great lipid solubility leading to fast onset (one to two minutes), has a short half-life (up to three hours) and limited histamine release. It is metabolized by the liver and its excretion is not affected by the kidneys. Those characteristics allow fentanyl to be versatile and be used in many different scenarios in the ICU. Despite those advantages, concerns have been raised regarding adipose tissue accumulation, tachyphylaxis, CYP3A4 interaction and chest wall rigidity, particularly when on high doses.

Hydromorphone is an alternative analgesic agent. It is a semisynthetic morphine derivate that can be five to ten times more potent than morphine. It also has a fast onset (up to 10 minutes), a short half-life (up to three hours) and is less renally excreted than morphine. Some concerns have been raised regarding the accumulation of hydromorphone metabolites including hydromorphone-3-glucuronide, which can lead to neuroexcitatory effects and delirium. A few retrospective studies compared fentanyl and hydromorphone in the critical care setting. Due to the retrospective nature, small size of the studies and several imbalances in the groups, no significant conclusion can be drawn regarding the benefits and risks of fentanyl versus hydromorphone. However, the largest and most recent retrospective study, showed no difference in 28-day mechanical ventilation free days and death during mechanical ventilation.

Opioids currently used for analgosedation in mechanically ventilated ICU patients include morphine, fentanyl and hydromorphone. The selection of a specific agent as standard-of-care is determined by primary ICU team preference, logistics, patient characteristics and experience. Although small differences may affect the decision of one over the other, dosage reduction and close monitoring are used rather than switching to an alternative in most cases. Whether or not either of these agents afford additional meaningful clinical benefits, advantages or contribute to meaningful clinical outcomes has not been fully established in available literature and represents the basis for performing this clinical pilot study. Therefore, the investigators propose to study the use of fentanyl and hydromorphone in the critically ill population on mechanical ventilation due to the paucity of data comparing both medications head-to-head and their widespread use.

Between November 2025 and April 2026, all patients on mechanical ventilation admitted to the medical intensive care units (MICU) and Finard intensive care unit (FICU - medical and surgical ICU) at Beth Israel Deaconess Medical Center who are 18 years or older will be enrolled. The study will be pragmatic and randomization will be in two clusters. The MICU and the FICU will be randomized to an initial opioid (fentanyl or hydromorphone) in three-months blocks. The assigned opioid will be used as the first line agent of choice for analgosedation. The assigned opioid will be switched at the end of the three-months block. Since the study has a 6 months duration, each ICU will have 3 months with each opioid as first line for analgosedation. The investigators anticipate that 300 patients will be required for sample size.

Conditions

Mechanical Ventilation; Sedation and Analgesia; Critical Care, Intensive Care

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Fentanyl as first line agent

Patients in an ICU on a three-month period randomized to Fentanyl will have Fentanyl used as suggested first-line therapy for analgosedation, when clinically warranted.

Group Type: EXPERIMENTAL

fentanyl

Intervention Type: DRUG

Suggested initial continuous infusion

• Route: Intravenous
• Dose: 0-200 mcg/hr (max 1,440 MME/day)
• Initial dose: 50mcg/hr
• Concentration: 50 mcg/mL
• Bolus: 50-200mcg up to every 5 minutes as needed
• Continuous infusion adjustment: Increase in the continuous infusion if sedation not at goal after 3 bolus doses, increase by 25 mcg/hr every 60 minutes

Titration of dose, initial dose, adjustments and bolus are just suggested. The primary team is allowed to modify them based on clinical judgement.

Hydromorphone as first line agent

Patients in an ICU on a three-month period randomized to Hydromorphone will have Hydromorphone used as suggested first-line therapy for analgosedation, when clinically warranted.

Group Type: EXPERIMENTAL

Hydromorphone

Intervention Type: DRUG

Suggested initial continuous infusion

• Route: Intravenous
• Dose: 0-3 mg/hr (max 1,440 MME/day)
• Initial dose: 0.5mg/hr
• Concentration: 0.2 mg/mL
• Bolus: 0.5-2mg up to every 5 minutes as needed
• Continuous infusion adjustment: Increase in the continuous infusion if sedation not at goal after 3 bolus doses, increase by 0.25 mg/hr every 60 minutes

Titration of dose, initial dose, adjustments and bolus are just suggested. The primary team is allowed to modify them based on clinical judgement.

Interventions

fentanyl

Suggested initial continuous infusion

• Route: Intravenous
• Dose: 0-200 mcg/hr (max 1,440 MME/day)
• Initial dose: 50mcg/hr
• Concentration: 50 mcg/mL
• Bolus: 50-200mcg up to every 5 minutes as needed
• Continuous infusion adjustment: Increase in the continuous infusion if sedation not at goal after 3 bolus doses, increase by 25 mcg/hr every 60 minutes

Titration of dose, initial dose, adjustments and bolus are just suggested. The primary team is allowed to modify them based on clinical judgement.

Intervention Type: DRUG

Hydromorphone

Suggested initial continuous infusion

• Route: Intravenous
• Dose: 0-3 mg/hr (max 1,440 MME/day)
• Initial dose: 0.5mg/hr
• Concentration: 0.2 mg/mL
• Bolus: 0.5-2mg up to every 5 minutes as needed
• Continuous infusion adjustment: Increase in the continuous infusion if sedation not at goal after 3 bolus doses, increase by 0.25 mg/hr every 60 minutes

Titration of dose, initial dose, adjustments and bolus are just suggested. The primary team is allowed to modify them based on clinical judgement.

Intervention Type: DRUG

Other Intervention Names

Dilaudid

Eligibility Criteria

Inclusion Criteria

• Admitted to either MICU A, B, C or FICU at Beth Israel Deaconess Medical Center
• Requiring mechanical ventilation
• Felt by primary team to require opioid infusion for analgosedation

Exclusion Criteria

• Age < 18 years old
• Do not intubate orders prior to enrollment
• Comfort measures only
• Contraindication to fentanyl or hydromorphone

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Elias Baedorf Kassis

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elias N Baedorf-Kassis, MD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Valerie Goodspeed, MPH

Role: CONTACT

vgoodspe@bidmc.harvard.edu

6176328055

Eduardo MH Padrao, MD

Role: CONTACT

epadrao@bidmc.harvard.edu

8603716289

Facility Contacts

Elias Baedorf Kassis, MD

Role: primary

Valerie Goodspeed

Role: backup

Other Identifiers

2025P000456

Identifier Type: -

Identifier Source: org_study_id