Dexmedetomidine and Liver Transplantation

NCT03770130 | Completed Early Phase 1

• 1 other identifier: DAS-OLT Trial
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Incidence of early allograft dysfunction (EAD) following surgery

  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.

  7 days

Secondary Outcomes (5)

• Incidence of postoperative acute kidney injury (AKI) during the postoperative day 1-7

  7 days

• Incidence of acute respiratory distress syndrome (ARDS) during the postoperative day 1-7

  7 days

• 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

Study Arms (2)

Dexmedetomidine treatment group

EXPERIMENTAL

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.

Drug: Dexmedetomidine

Control group

PLACEBO COMPARATOR

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.

Drug: Saline

Interventions

Dexmedetomidine DRUG

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

Dexmedetomidine treatment group

Saline DRUG

Saline, a kind of crystalloid widely used in clinical treatment

Control group

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Severe renal dysfunction (undergoing renal replacement therapy before surgery)
• Severe pulmonary dysfunction (including pneumonia, atelectasis, pleural effusion, acute lung injury or ARDS)
• 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)
• Known allergy or intolerance to trial medication
• Refusal to participate in the study
• Participation in other clinical trials within 30 days prior to randomisation.
• Retransplantation
• Multiple organ transplantation
• Other reasons that are considered unsuitable for study participation by the responsible surgeon or anaesthetist (reasons must be documented in the case report form \[CRF\])

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Renji Hospital, Shanghai Jiao Tong University, School of Medicine

Shanghai, 200127, China

Location

Related Publications (2)

• 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.

  PMID: 38768468 DERIVED

• 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.

  PMID: 32591004 DERIVED

MeSH Terms

Interventions

Dexmedetomidine; Sodium Chloride

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: December 10, 2018
• Study Start: January 14, 2019
• Primary Completion: October 31, 2022
• Study Completion: December 31, 2022
• Last Updated: August 21, 2023

Record last verified: 2023-08

Locations

CN (1)