Dexmedetomidine and Liver Transplantation

Early Phase 1

Completed

• Conditions: Dexmedetomidine, Liver Transplantation, Allograft Function, Survival
• Interventions: Drug: Saline; Drug: Dexmedetomidine

• Registration Number: NCT03770130
• Lead Sponsor: RenJi Hospital

Brief Summary

1.1. Background 1.1.1. Perioperative ischaemia/reperfusion (I/R) injury during liver transplantation is strongly associated with early allograft dysfunction, graft loss, and mortality.

1.1.2. Hepatic I/R injury also causes remote damage to other organs including the renal and pulmonary systems.

1.1.3. Dexmedetomidine, a selective α2-adrenoceptor agonist which is widely used as an adjuvant to general anaesthesia, has been widely shown in preclinical studies to provide organoprotection by ameliorating the effects of I/R injury in a range of tissues (including the liver). However, prospective clinical evidence of any potential benefits in improving outcomes in liver transplantation is lacking.

1.2. Objectives 1.2.1. To investigate the hypothesis that perioperative treatment with dexmedetomidine reduces the incidence of early allograft dysfunction and primary graft non-function in deceased donor liver transplantation.

1.2.2. The impact of dexmedetomidine on postoperative renal and pulmonary function will also be examined.

1.3. Study Design This is a prospective, single-centre, randomised, parallel-group study.

1.4. Setting Departments of Anesthesiology, Renji Hosptial, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.

1.5. Patients 200 patients (18-65 years) scheduled to undergo liver transplantation under general anaesthesia.

1.6 Intervention 1.6.1. For the patients in the treatment group, a loading dose of dexmedetomidine will be given after induction of anaesthesia (1μg/kg over 10 min) followed by a continuous infusion (0.5μg/kg /h) until the end of surgery.

1.6.2. For patients in the placebo group, an equal volume loading dose of 0.9% saline will be given after the induction of anaesthesia followed by an equal volume continuous infusion until the end of surgery.

1.6.3. All other supplements, e.g. opioids, sedatives and muscle relaxant, will be identical in the both arms and administered according to routine clinical practice.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-12-06
• Study First Submitted QC: 2018-12-06
• Study First Posted: 2018-12-10
• Study Start: 2019-01-14
• Primary Completion: 2022-10-31
• Study Completion: 2022-12-31
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-16
• Last Update Posted: 2023-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 330

Inclusion Criteria

1. Age 18-65 years
2. Scheduled to undergo allogenic liver transplant(DCD/DBD) surgery under general anaesthesia
3. Patients should meet the UCSF criteria
4. Agree to participate and give written informed consent

Read More

Exclusion Criteria

1. Severe renal dysfunction (undergoing renal replacement therapy before surgery)
2. Severe pulmonary dysfunction (including pneumonia, atelectasis, pleural effusion, acute lung injury or ARDS)
3. Severe circulatory instability (severe coronary artery disease, unstable angina, left ventricular ejection fraction < 30%, sick sinus syndrome, severe sinus bradycardia [< 50 bpm], second-degree or greater atrioventricular block)
4. Known allergy or intolerance to trial medication
5. Refusal to participate in the study
6. Participation in other clinical trials within 30 days prior to randomisation.
7. Retransplantation
8. Multiple organ transplantation
9. Other reasons that are considered unsuitable for study participation by the responsible surgeon or anaesthetist (reasons must be documented in the case report form [CRF])

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Saline	Anaesthesia will be maintained with sevoflurane inhalation, of which the concentration will be adjusted to maintain the BIS value between 40 and 60. Muscle relaxation will be maintained with rocuronium or cisatracurium. Analgesia will be maintained with remifentanil (administered via continuous infusion), sufentanil (administered via continuous infusion or intermittent injection), or fentanyl (administered via intermittent injection). In addition to this, patients will receive an equal volume initial loading dose of 0.9% saline over 10 min after the induction of anaesthesia followed by an equal volume continuous infusion until the end of surgery.
Dexmedetomidine treatment group	Dexmedetomidine	Anaesthesia will be maintained with sevoflurane inhalation, of which the concentration will be adjusted to maintain the BIS value between 40 and 60. Muscle relaxation will be maintained with rocuronium or cisatracurium. Analgesia will be maintained with remifentanil (administered via continuous infusion), sufentanil (administered via continuous infusion or intermittent injection), or fentanyl (administered via intermittent injection). In addition to this, patients will receive an initial loading dose of dexmedetomidine of 1μg/kg over 10 min after the induction of anaesthesia followed by a continuous infusion of 0.5μg/kg/h until the end of surgery.

Primary Outcome Measures

Name	Time	Method
Incidence of early allograft dysfunction (EAD) following surgery	7 days	Defined according to Olthoff's criteria published in 2010: (1) bilirubin ≥ 10mg/dL on day 7; or (2) INR \> 1.6 on day 7; or (3) AST/ ALT \> 2000IU/L within first 7 days.

Secondary Outcome Measures

Name	Time	Method
Incidence of postoperative acute kidney injury (AKI) during the postoperative day 1-7	7 days	Defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria published in 2012: (1) Increase in serum creatinine by ≥ 0.3mg/dL within 48 hours; or (2) increase in serum creatinine to 1.5 times baseline or more within past 7 days; or (3) urine output \< 0.5mL/kg/h for 6 hours.
Incidence of acute respiratory distress syndrome (ARDS) during the postoperative day 1-7	7 days	Defined according to Berlin modification of the American European Consensus Committee (AECC) definitions published in 2012: (1) Acute onset (within one week of known insult); and (2) bilateral opacities on CXR (not explained by effusions, nodules, or collapse); and (3) respiratory failure not fully explained by cardiac failure or fluid overload; and (4) Severity graded by PaO2/ FIO2 ratio with PEEP 5cmH2O i. Mild 300 ≥ PaO2/ FIO2 \> 200; ii. Moderate 200 ≥ PaO2/ FIO2 \> 100; iii. Severe 100 ≥ PaO2/ FIO2.
Incidence of graft failure and retransplantation rate during 3 year follow up period.	3 years
All cause mortality in the 3 year follow-up period.	3 years
Incidence of primary graft non-function (PNF)	30 days	Defined as graft loss, retransplantation, or patient death due to graft non-function in first 30 days (excluding non-function secondary to hepatic artery thrombosis, biliary complications, or recurrent hepatic disease).

Trial Locations

Locations (1)

Renji Hospital, Shanghai Jiao Tong University, School of Medicine; 🇨🇳 Shanghai, China