Vasoplegic SyndromePhase 4NCT04054999

Methylene Blue vs Cyanokit for Intraoperative Vasoplegic Syndrome in Liver Transplant Patients

A Phase 4 study testing Hydroxocobalamin and Methylene Blue in people with Vasoplegic Syndrome and Liver Transplant; Complications, run by Mayo Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study will evaluate if Hydroxocobalamin may be a new and possibly superior treatment for refractory vasoplegic syndrome during liver transplant surgery. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Vasoplegic Syndrome, Liver Transplant; Complications
What is being tested?: Hydroxocobalamin and Methylene Blue
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 19 participants
Where: 1 siteUnited States
Study dates: 30 Nov 2019to 27 Feb 2024
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Patients scheduled to undergo liver transplantation
Patients able to read and understand consent document (if patient is unable to provide an informed consent, the Legally Authorized Representative will be ask to consent on behalf of the patient).
SVR lower than 500 dynes-sec/cm-5 intraoperatively (this criterion must be met after consent intraoperatively)

Trial locations and contacts

1 site in 1 country.

United States1 site

Mayo Clinic in Florida
Jacksonville, Florida, 32224

Other trials in United States

About this study

Official title: The Efficacy of Intravenous Hydroxocobalamin Versus Methylene Blue as Treatment for Intraoperative Vasoplegic Syndrome in Liver Transplant Patients

This study will evaluate if Hydroxocobalamin may be a new and possibly superior treatment for refractory vasoplegic syndrome during liver transplant surgery.

Conditions: Vasoplegic Syndrome, Liver Transplant; Complications
Being tested: Hydroxocobalamin, Methylene Blue
Keywords: hydroxocobalamin, methylene blue
Medical subject headings: Vasoplegia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

HydroxocobalaminDrug
Hydroxocobalamin (Cyanokit): 5g IV infusion over 15 minutes
Methylene BlueDrug
Methylene blue (PROVAYBLUETM), 2 mg/kg IV bolus administered over 15 minutes

Study groups in NCT04054999
Study group	Role	What they receive
Cyanokit	Experimental	Single dose intraoperatively of Hydroxocobalamin (Cyanokit): 5g IV infusion over 15 minutes Receives: Drug: Hydroxocobalamin
Methylene Blue	Active comparator	Single dose intraoperatively of Methylene blue (PROVAYBLUETM), 2 mg/kg IV bolus administered over 15 minutes Receives: Drug: Methylene Blue

What is being measured

The primary outcome is the main question the study is designed to answer.

Systemic Vascular Resistance (SVR)
SVR refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature. Measured during surgery at 15, 30, 60, 90 and 120 minutes after initiation of treatment.
Measured: 15, 30, 60, 90 and 120 minutes after initiation of treatment
Systolic Blood Pressure
Systolic blood pressure (top number of blood pressure reading). Measured during surgery at 15, 30, 60, 90 and 120 minutes after initiation of treatment.
Measured: 15, 30, 60, 90 and 120 minutes after initiation of treatment
Diastolic Blood Pressure
Diastolic blood pressure (bottom number of blood pressure reading). Measured during surgery at 15, 30, 60, 90 and 120 minutes after initiation of treatment.
Measured: 15, 30, 60, 90 and 120 minutes after initiation of treatment
Vasopressin
Vasopressin as measured by the total amount of vasopressors administered. Measured at 15, 30, 60, 90 and 120 minutes after initiation of treatment.
Measured: 15, 30, 60, 90 and 120 minutes after initiation of treatment

Secondary outcomes (3)

Post-operative Intensive Care Unit (ICU) Length of Stay
Total number of days subjects were admitted to the ICU
Measured: Up to 30 days after surgery
Hospital Length of Stay
Total number of days subjects were admitted to the hospital
Measured: Up to 30 days after surgery
Post-operative Complications
The number of subjects to experience a death, cardiopulmonary event, Acute Kidney injury (AKI), Myocardial infarctions (MI), Stroke or Surgical and medical procedures - Other.
Measured: Up to 30 days after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Nov 201927 Feb 2024

First posted13 Aug 2019
Study start30 Nov 2019
Primary completion27 Feb 2023
Study completion27 Feb 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Vasoplegic SyndromeStudies of the same condition, open and under way.
More trials run by Mayo ClinicThe 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: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Randomized, Open-Label, pilot study to describe the efficacy of hydroxocobalamin vs methylene blue
Masking: None (open label)
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04054999
Sponsor's protocol ID: 18-006247
Status last verified: Jun 2024
First submitted: 12 Aug 2019
Last updated: 24 Jun 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Vasoplegic Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Efficacy of Intravenous Hydroxocobalamin Versus Methylene Blue as Treatment for Intraoperative Vasoplegic Syndrome in Liver Transplant Patients
ClinicalTrials.gov ID: NCT04054999
Acronym / sponsor ID: 18-006247
Conditions: Vasoplegic Syndrome, Liver Transplant; Complications
Keywords: hydroxocobalamin, methylene blue
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 19 participants (actual)
Lead sponsor: Mayo ClinicUniversity, hospital or other
Study start: 30 Nov 2019 (actual)
Primary completion: 27 Feb 2023 (actual)
Study completion: 27 Feb 2024 (actual)
First posted: 13 Aug 2019 (actual)
Results: Posted 24 Jun 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will evaluate if Hydroxocobalamin may be a new and possibly superior treatment for refractory vasoplegic syndrome during liver transplant surgery.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: Randomized, Open-Label, pilot study to describe the efficacy of hydroxocobalamin vs methylene blue

Arm	Type	Receives
Cyanokit	Experimental	Drug: HydroxocobalaminSingle dose intraoperatively of Hydroxocobalamin (Cyanokit): 5g IV infusion over 15 minutes
Methylene Blue	Active comparator	Drug: Methylene BlueSingle dose intraoperatively of Methylene blue (PROVAYBLUETM), 2 mg/kg IV bolus administered over 15 minutes

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

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
HydroxocobalaminHydroxocobalamin (Cyanokit): 5g IV infusion over 15 minutes	Drug	Cyanokit
Methylene BlueMethylene blue (PROVAYBLUETM), 2 mg/kg IV bolus administered over 15 minutes	Drug	Methylene Blue

Primary outcome

Systemic Vascular Resistance (SVR)
Time frame: 15, 30, 60, 90 and 120 minutes after initiation of treatment
SVR refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature. Measured during surgery at 15, 30, 60, 90 and 120 minutes after initiation of treatment.
Systolic Blood Pressure
Time frame: 15, 30, 60, 90 and 120 minutes after initiation of treatment
Systolic blood pressure (top number of blood pressure reading). Measured during surgery at 15, 30, 60, 90 and 120 minutes after initiation of treatment.
Diastolic Blood Pressure
Time frame: 15, 30, 60, 90 and 120 minutes after initiation of treatment
Diastolic blood pressure (bottom number of blood pressure reading). Measured during surgery at 15, 30, 60, 90 and 120 minutes after initiation of treatment.
Vasopressin
Time frame: 15, 30, 60, 90 and 120 minutes after initiation of treatment
Vasopressin as measured by the total amount of vasopressors administered. Measured at 15, 30, 60, 90 and 120 minutes after initiation of treatment.

3 secondary outcomes

Post-operative Intensive Care Unit (ICU) Length of Stay
Time frame: Up to 30 days after surgery
Hospital Length of Stay
Time frame: Up to 30 days after surgery
Post-operative Complications
Time frame: Up to 30 days after surgery

Results and safety

Results posted to the registry on 24 Jun 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cyanokit	9	9
Methylene Blue	10	10

Primary outcome: Systemic Vascular Resistance (SVR)

Time frame: 15, 30, 60, 90 and 120 minutes after initiation of treatment. Median (Full Range). Unit: dyne*sec/cm^5

Measure	Cyanokit n = 9	Methylene Blue n = 9
15 minutes	480 (350 to 850)	410 (380 to 570)
30 minutes	588 (330 to 770)	420 (310 to 760)
60 minutes	650 (390 to 1170)	480 (300 to 940)
90 minutes	571 (430 to 990)	530 (330 to 610)
120 minutes	543 (440 to 1060)	415 (340 to 670)

Population analysed: Data was not collected nor analyzed at all for one participant in the Methylene Blue arm. The number of participants analyzed at each time point differs due to some participants completing their surgery earlier than others. Those participants were out of the surgical room by those time points and data was not collected nor analyzed.

Primary outcome: Systolic Blood Pressure

Time frame: 15, 30, 60, 90 and 120 minutes after initiation of treatment. Median (Full Range). Unit: Millimeters of Mercury

Measure	Cyanokit n = 9	Methylene Blue n = 10
15 minutes	109 (96 to 130)	110 (63 to 120)
30 minutes	113 (97 to 147)	101 (87 to 130)
60 minutes	120 (95 to 158)	111 (92 to 145)
90 minutes	129 (104 to 152)	111 (90 to 162)
120 minutes	116 (83 to 149)	109 (101 to 161)

Population analysed: The number of participants analyzed at each time point differs due to some participants completing their surgery earlier than others. Those participants were out of the surgical room by those time points and data was not collected nor analyzed.

Primary outcome: Diastolic Blood Pressure

Time frame: 15, 30, 60, 90 and 120 minutes after initiation of treatment. Median (Full Range). Unit: Millimeters of Mercury

Measure	Cyanokit n = 9	Methylene Blue n = 10
15 minutes	58 (40 to 66)	55 (39 to 62)
30 minutes	57 (43 to 72)	55 (41 to 68)
60 minutes	61 (39 to 73)	55 (47 to 78)
90 minutes	60 (42 to 72)	57 (50 to 70)
120 minutes	59 (47 to 78)	57 (49 to 98)

Primary outcome: Vasopressin

Time frame: 15, 30, 60, 90 and 120 minutes after initiation of treatment. Median (Full Range). Unit: milli-units/kg/min

Measure	Cyanokit n = 9	Methylene Blue n = 10
15 minutes	0.04 (0.00 to 0.17)	0.04 (0.00 to 3.71)
30 minutes	0.04 (0.00 to 0.13)	0.04 (0.00 to 3.37)
60 minutes	0.00 (0.00 to 0.13)	0.02 (0.00 to 0.37)
90 minutes	0.00 (0.00 to 0.13)	0.00 (0.00 to 0.37)
120 minutes	0.00 (0.00 to 0.11)	0.00 (0.00 to 0.31)

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events were collected from baseline until hospital discharge, approximately two months.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cyanokit	0 of 9 (0%)	1 of 9 (11.1%)	1 of 9
Methylene Blue	0 of 10 (0%)	2 of 10 (20%)	1 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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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.

Sher-Lu Pai, MD principal investigator

Mayo Clinic

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Hydroxocobalamin and Methylene Blue in people with Vasoplegic Syndrome and Liver Transplant; Complications, run by Mayo Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 24 Jun 2024. 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 United States. 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. 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?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Systemic Vascular Resistance (SVR) (time frame: 15, 30, 60, 90 and 120 minutes after initiation of treatment). The study lists 4 primary outcomes in all. 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 NCT04054999.

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 24 Jun 2024.