Fentanyl Versus Hydromorphone in Patients on Mechanical Ventilation

NCT07224620 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 2025P000456
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Fentanyl; Hydromorphone; Mechanical ventilation; Intensive Care Unit; ICU; Analgosedation; Analgesia; Sedation

Outcome Measures

Primary Outcomes (1)

• Difference in daily MME dose received during mechanical ventilation period.

  The daily MME dose will be calculated using all the opioid doses received during the day. The outcome will be obtained from the days patients were on mechanical ventilation. It will include not only the intervention medication, but also the additional boluses and alternate opioids, including cross-over drug. The doses will be converted into MME.

  Assessed from enrollment (baseline) censored at day 28

Secondary Outcomes (10)

• All cause 28-day hospital mortality

  28 days after enrollment censored at hospital discharge

• Days alive and free of mechanical ventilation at day 28

  28 days after enrollment censored at hospital discharge

• Days alive and free of ICU at day 28

  28 days after enrollment censored at hospital discharge

• Days alive and free of vasopressors at day 28

  28 days after enrollment censored at hospital discharge

• Difference in average daily dose of morphine milligram equivalent required during the first 28 days

  28 days after enrollment censored at hospital discharge

Other Outcomes (4)

• Requirement of adjunctive analgesia or sedation medications

  Measured through 28 days after enrollment.

• Patient-ventilator respiratory mechanics

  Through mechanical ventilation period in the first 3 and 7 days

• Mean difference in total MME dose received during the first 24 hours, first 3 days

  Day 1, 3 and 7 after enrollment

Study Arms (2)

Fentanyl as first line agent

EXPERIMENTAL

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.

Drug: fentanyl

Hydromorphone as first line agent

EXPERIMENTAL

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.

Drug: Hydromorphone

Interventions

fentanyl 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.

Fentanyl as first line agent

Hydromorphone 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.

Also known as: Dilaudid

Hydromorphone as first line agent

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Agnosia

Interventions

Fentanyl; Hydromorphone

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Elias N Baedorf-Kassis, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: Randomization will occur at the level of the ICU, rather than for each individual patient. Cluster I (MICU A, B, C) and cluster II (FICU) will be randomized to start from a period with fentanyl or hydromorphone and after 3 months will be crossed over to the other group. The process will be repeated during the study period. Cluster cross-over are planned to be 3 months to avoid seasonal variability. The investigators plan to start the enrollment in the middle of a season, so that the clusters have 1.5 months of each season. No washout period is planned.

Study Record Dates

• First Submitted: October 28, 2025
• First Posted: November 4, 2025
• Study Start: November 3, 2025
• Primary Completion: May 1, 2026
• Study Completion: June 1, 2026
• Last Updated: May 29, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Individual participant data that underlie the results will be available starting 12 months after publication of the main results paper and will remain available for 5 years after that date
• Access Criteria: Who can access the data: Data will be made available to researchers whose proposed use of the data has been approved by the lead trial investigators. Types of analyses: For any purpose that facilitates advancement of the field Mechanisms of data availability: With investigator support and IRB approval, after approval of a proposal, with a signed data access agreement

Locations

US (1)