Dexmedetomidine, Liver Transplantation, Allograft Function, SurvivalEarly Phase 1NCT03770130
Dexmedetomidine and Liver Transplantation
A Early Phase 1 study testing Dexmedetomidine and Saline in people with Dexmedetomidine, Liver Transplantation, Allograft Function, Survival, run by RenJi Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Dexmedetomidine, Liver Transplantation, Allograft Function, Survival
- What is being tested?
- Dexmedetomidine and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 330 participants
- Where
- 1 siteChina
- Study dates
- 14 Jan 2019to 31 Dec 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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])
Trial locations and contacts
1 site in 1 country.
China1 site
Renji Hospital, Shanghai Jiao Tong University, School of Medicine
Shanghai, 200127
About this study
Official title: Evaluation of the Impact of Dexmedetomidine on Allograft Function Recovery and Survival Following Liver Transplantation: A Randomised Control Trial
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.
Read more
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.
- Being tested
- Dexmedetomidine, Saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Dexmedetomidine, a selective α2-adrenoceptor agonist which is widely used as an adjuvant to general anaesthesia
SalineDrug
Saline, a kind of crystalloid widely used in clinical treatment
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7 days
Secondary outcomes (5)
Incidence of postoperative acute kidney injury (AKI) during the postoperative day 1-7
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.
Measured: 7 days
Incidence of acute respiratory distress syndrome (ARDS) during the postoperative day 1-7
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.
Measured: 7 days
Incidence of graft failure and retransplantation rate during 3 year follow up period.
Measured: 3 years
All cause mortality in the 3 year follow-up period.
Measured: 3 years
Incidence of primary graft non-function (PNF)
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).
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2018
- Study start14 Jan 2019
- Primary completion31 Oct 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Dexmedetomidine, Liver Transplantation, Allograft Function, SurvivalStudies of the same condition, open and under way.
- More trials run by RenJi HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 330 participants (actual)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03770130
- Sponsor's protocol ID
- DAS-OLT Trial
- Status last verified
- Aug 2023
- First submitted
- 6 Dec 2018
- Last updated
- 21 Aug 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 38768468Ni 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.
PubMed 32591004
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Impact of Dexmedetomidine on Allograft Function Recovery and Survival Following Liver Transplantation: A Randomised Control Trial
- ClinicalTrials.gov ID
- NCT03770130
- Acronym / sponsor ID
- DAS-OLT Trial
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 330 participants (actual)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Study start
- 14 Jan 2019 (actual)
- Primary completion
- 31 Oct 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 10 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine treatment group | Experimental | Drug: DexmedetomidineAnaesthesia 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. |
| Control group | Placebo comparator | Drug: SalineAnaesthesia 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexmedetomidineDexmedetomidine, a selective α2-adrenoceptor agonist which is widely used as an adjuvant to general anaesthesia | Drug | Dexmedetomidine treatment group |
| SalineSaline, a kind of crystalloid widely used in clinical treatment | Drug | Control group |
Primary outcome
Incidence of early allograft dysfunction (EAD) following surgery
Time frame: 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.
5 secondary outcomes
Incidence of postoperative acute kidney injury (AKI) during the postoperative day 1-7
Time frame: 7 days
Incidence of acute respiratory distress syndrome (ARDS) during the postoperative day 1-7
Time frame: 7 days
Incidence of graft failure and retransplantation rate during 3 year follow up period.
Time frame: 3 years
All cause mortality in the 3 year follow-up period.
Time frame: 3 years
Incidence of primary graft non-function (PNF)
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2023.
- Derived from this study: PubMed 38768468Yang 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.
- Derived from this study: PubMed 32591004Ni 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Dexmedetomidine and Saline in people with Dexmedetomidine, Liver Transplantation, Allograft Function, Survival, run by RenJi Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of early allograft dysfunction (EAD) following surgery (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03770130, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2023.