Dexmedetomidine and Liver Transplantation

NCT ID: NCT03770130

Last Updated: 2023-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 330 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-14
• Study Completion Date: 2022-12-31

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.

Conditions

Dexmedetomidine, Liver Transplantation, Allograft Function, Survival

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dexmedetomidine treatment group

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.

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: DRUG

Dexmedetomidine, a selective α2-adrenoceptor agonist which is widely used as an adjuvant to general anaesthesia

Control group

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.

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

Saline, a kind of crystalloid widely used in clinical treatment

Interventions

Dexmedetomidine

Dexmedetomidine, a selective α2-adrenoceptor agonist which is widely used as an adjuvant to general anaesthesia

Intervention Type: DRUG

Saline

Saline, a kind of crystalloid widely used in clinical treatment

Intervention Type: DRUG

Eligibility Criteria

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

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])

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RenJi Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Renji Hospital, Shanghai Jiao Tong University, School of Medicine

Shanghai, , China

Countries

China

References

Yang L, Zhu L, Qi B, Zhang Y, Ni C, Zhang Y, Shi X, Xia Q, Masters J, Ma D, Yu W. Dexmedetomidine use during orthotopic liver transplantation surgery on early allograft dysfunction: a randomized controlled trial. Int J Surg. 2024 Sep 1;110(9):5518-5526. doi: 10.1097/JS9.0000000000001669.

Reference Type: DERIVED

PMID: 38768468 (View on PubMed)

Ni C, Masters J, Zhu L, Yu W, Jiao Y, Yang Y, Cui C, Yin S, Yang L, Qi B, Ma D. Study design of the DAS-OLT trial: a randomized controlled trial to evaluate the impact of dexmedetomidine on early allograft dysfunction following liver transplantation. Trials. 2020 Jun 26;21(1):582. doi: 10.1186/s13063-020-04497-7.

Reference Type: DERIVED

PMID: 32591004 (View on PubMed)

Other Identifiers

DAS-OLT Trial

Identifier Type: -

Identifier Source: org_study_id