Fentanyl Versus Hydromorphone as First Line Strategy in Patients on Mechanical Ventilation, a Pilot Pragmatic Randomized Superiority Clinical Trial: the FenHydro Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 319
- 试验地点
- 1
- 主要终点
- Difference in daily MME dose received during mechanical ventilation period.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Age < 18 years old
- •Do not intubate orders prior to enrollment
- •Comfort measures only
- •Contraindication to fentanyl or hydromorphone
研究组 & 干预措施
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.
干预措施: fentanyl (Drug)
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.
干预措施: Hydromorphone (Drug)
结局指标
主要结局
Difference in daily MME dose received during mechanical ventilation period.
时间窗: Assessed from enrollment (baseline) censored at day 28
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.
次要结局
- 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)
- Percentage of time without coma and delirium during the ICU stay(Assessed from enrollment (baseline) censored at day 28)
- Days alive and free of restraints at 28 days(28 days after enrollment censored at hospital discharge)
- Daily Average number of Bowel Movements through ICU stay(Assessed from enrollment (baseline) censored at day 28)
- Need for tracheostomy during hospital stay or 28 days(Hospital stay or 28 days (whichever comes first))
- Days alive and out of hospital(28 days after enrollment censored at hospital discharge)
研究者
Elias Baedorf Kassis
MD
Beth Israel Deaconess Medical Center