Clinical trial NCT03770130: Dexmedetomidine and Liver Transplantation
Official title: Evaluation of the Impact of Dexmedetomidine on Allograft Function Recovery and Survival Following Liver Transplantation: A Randomised Control Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Dexmedetomidine, Liver Transplantation, Allograft Function, Survival
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2018-12-10
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 \[CRF\])

Primary outcomes:
measure: Incidence of early allograft dysfunction (EAD) following surgery
timeFrame: 7 days
Secondary outcomes:
measure: Incidence of postoperative acute kidney injury (AKI) during the postoperative day 1-7
timeFrame: 7 days
measure: Incidence of acute respiratory distress syndrome (ARDS) during the postoperative day 1-7
timeFrame: 7 days
measure: Incidence of graft failure and retransplantation rate during 3 year follow up period.
timeFrame: 3 years
measure: All cause mortality in the 3 year follow-up period.
timeFrame: 3 years
measure: Incidence of primary graft non-function (PNF)
timeFrame: 30 days
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiao Tong University, School of Medicine
Study officials:
References:
citation: 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.