The Evaluation of the Effectiveness and Safety of Nalbuphine Hydrochloride Injection for Analgesia in ICU Patients: A Multicenter, Randomized, Single-blinded, Parallel, Two-step Trial

Huazhong University of Science and Technology

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Respiratory Insufficiency

Treatments: Drug: Hydromorphone hydrochloride injection; Drug: Nalbuphine hydrochloride injection

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06785571

2023-0407

Details and patient eligibility

About

The analgesic effect of nalbuphine hydrochloride injection will be evaluated in a multicenter, randomized, single-blind, parallel, positive-controlled approach in two steps: step 1, to explore the optimal dosage of nalbuphine hydrochloride injection with 2 experimental arms and 1 positive control and step 2, to evaluate the effectiveness and safety of nalbuphine hydrochloride injection in mechanically ventilated ICU patients at a dosage determined in step 1 with the same positive control.

Enrollment: 204 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. ICU patients who are intubated are expected to require mechanical ventilation for more than 6h
2. patients or their guardians have a full understanding of the purpose and significance of this trial, and voluntarily participate in this clinical trial and sign an informed consent form

Exclusion criteria

1. Allergy or unsuitability to any composition of study drugs or propofol
2. Living expectancy of less than 48 hours
3. Neurological disorder and any other condition interfering with sedation assessment
4. Gastrointestinal obstruction
5. Asthmatic
6. Abdominal compartment syndrome
7. Serious hepatic dysfunction (CTP 10-15)
8. Acute kidney injury (KDIGO stage 2 or 3) or Chronic kidney disease with glomerular filtration rate (GFR) < 29 ml/min/1.73m2
9. Circulatory instability (the need for a continuous infusion of norepinephrine at ≥0.5 ug/kg/min to maintain proper blood pressure)
10. Need deep sedation or paralytics
11. Anticipation to receive operations (including tracheotomy)
12. Abuse of controlled substances or alcohol
13. Pregnancy, lactation, or an intention of gestation in 6 months
14. Inclusion in another interventional trial in the past 30 days
15. Other conditions deemed unsuitable to be included

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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204 participants in 5 patient groups

lower loading dose of Nalbuphine hydrochloride for step 1

Experimental group

Description:

Nalbuphine hydrochloride injection, a loading dose of 4 mg administered in 30 ±10 seconds, followed by a maintenance dose of 2.0mg/h (a recommended maintenance dose range of 1.0\~5.0mg/h)

Treatment:

Drug: Nalbuphine hydrochloride injection

higher loading dose of Nalbuphine hydrochloride for step 1

Experimental group

Description:

Nalbuphine hydrochloride injection, a loading dose of 6 mg administered in 30 ±10 seconds, followed by a maintenance dose of 2.0mg/h (a recommended maintenance dose range of 1.0\~5.0mg/h)

Treatment:

Drug: Nalbuphine hydrochloride injection

Hydromorphone hydrochloride injection for step 1

Active Comparator group

Description:

Hydromorphone hydrochloride injection: a maintenance dose of 0.5mg/h (a recommended maintenance dose range of 0.5\~3.0mg/h)

Treatment:

Drug: Hydromorphone hydrochloride injection

The optimal loading of Nalbuphine hydrochloride injection for step 2

Experimental group

Description:

Nalbuphine hydrochloride injection: a loading dose determined after step 1 administered in 30 ±10 seconds, followed by a maintenance dose of 2.0mg/h (a recommended maintenance dose range of 1.0\~5.0mg/h)

Treatment:

Drug: Nalbuphine hydrochloride injection

Hydromorphone hydrochloride injection for step 2

Active Comparator group

Description:

Hydromorphone hydrochloride injection: a maintenance dose of 0.5mg/h (a recommended maintenance dose range of 0.5\~3.0mg/h)

Treatment:

Drug: Hydromorphone hydrochloride injection