Vasoplegic SyndromePhase 4RaGuSNCT04440085
RaGuS Trial by Postoperative Patients
A Phase 4 study testing Midodrine Hydrochloride in people with Vasoplegic Syndrome and Sirs Due to Noninfectious Process Without Organ Dysfunction, run by Bürgerspital Solothurn.
Trial summary
Vasoplegic syndrome is characterized clinically by reduced systemic vascular resistance and normal or increased cardiac output. It is principally observed in cardiovascular and orthopedic interventions and is characterized by a systemic inflammatory response with the inability of the vascular endothelial muscles to… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Vasoplegic Syndrome, Sirs Due to Noninfectious Process Without Organ Dysfunction, Orthostatic Hypotension
- What is being tested?
- Midodrine Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 14 Sep 2020to 14 Sep 2021
- Phase
- Phase 4
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Over 18 years of age
- Need of vasoactive drugs after three hours from arrival and adequate volume recovery.
Who cannot join
- Signs of infection (anamnesis or pro-calcitonin > 0.2 with leukocytosis, CRP and/or fever)
- Serum lactate > 2mmol/l
- Mechanical ventilation
- Therapeutic restrictions or comfort measures at arrival
- "de novo" or acute on chronic heart failure (Reduction of known ejection fraction for more than 20 percent, signs of acute lung edema)
- Pregnant
- Patients with digoxin treatment or history of glaucoma.
- History of midodrine allergy, pheochromocytoma, thyrotoxicosis, tachyarrhythmias or ventricular fibrillation.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: RANDOMIZED CASE-CONTROLLED TRIAL ASSESSING MIDODRINE (GUTRON®) IN POSTOPERATIVE VASOPLEGIC PATIENTS
Vasoplegic syndrome is characterized clinically by reduced systemic vascular resistance and normal or increased cardiac output. It is principally observed in cardiovascular and orthopedic interventions and is characterized by a systemic inflammatory response with the inability of the vascular endothelial muscles to contract and a resistance to the action of vasoactive drugs. This event extends the length of stay in the critical care area due to the need of vasoactive drugs.
The investigators aim to assess the standardized application of midodrine in postoperative patients without sepsis and need of vasoactive drugs in order to reduce the length of stay in critical care area and for extension in hospital.
Read the detailed description
Midodrine is an alpha 1 receptor agonist used usually in cases of hypotension helping to increase blood pressure. The main indication is orthostatic hypotension but there are other clinical conditions where this medicament is often used like hypotension by dialysis, hepatorenal syndrome and after carotid artery stenting.
Vasoplegic syndrome coul be interpreted as a variant of orthostatic hypotension that happens usually after surgical interventions. It produces a loss of systemic vascular resistance due to inflammatory reaction without any signs of infection.
The investigators aim to conduct a randomized, double-blind, single-center, placebo-controlled study of midodrine in patients who present postoperative vasoplegia with no active signs of sepsis but need of vasoactive drugs (Noradrenalin).
- Conditions
- Vasoplegic Syndrome, Sirs Due to Noninfectious Process Without Organ Dysfunction, Orthostatic Hypotension
- Being tested
- Midodrine Hydrochloride, Placebo
- Keywords
- Midodrine, Vasoplegic syndrome, Noradrenaline, SIRS
- Medical subject headings
- Vasoplegia, Hypotension, Orthostatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Midodrine HydrochlorideDrug
All patients become standard care resuscitation treatment using liquids and vasoactive drugs in order to get a median arterial pressure ≥ 65 mmHg. Midodrine will be administered according to the evolution of the patient's mean pressure.
PlaceboDrug
All patients become standard care resuscitation treatment using liquids and vasoactive drugs in order to get a median arterial pressure ≥ 65 mmHg. Placebo will be administered according to the evolution of the patient's mean pressure.
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Active comparator | Midodrine will be administered every 8 hours, increasing the dose gradually until a maximum of 30 mg a day is reached. It will be given orally in the following sequence: 2.5 mg - 5 mg - 7.5 mg - 10 mg. The target standard perfusion pressure for all the patients will be a mean arterial pressure (MAP) > 65 mmHg, with unchanged dose of midodrine after target pressure is reached. If the pressure continues to increase, the same sequence will be followed for dose de-escalation. Receives: Drug: Midodrine Hydrochloride |
| Control group | Placebo comparator | By placebo group will be followed the same strategy.The target standard perfusion pressure for all the patients will be a mean arterial pressure (MAP) > 65 mmHg, with unchanged dose of placebo after target pressure is reached. If the pressure continues to increase, the same sequence will be followed for dose de-escalation. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time
Hours from initiation of treatment with midodrine to discharge from critical care area
Measured: aproximately 2 days
Secondary outcomes (3)
Length of stay
days in critical care area and hospital
Measured: aproximately 7 days
Vasopresors
Noradrenalin needed doses
Measured: aproximately 2 days
Fluid balance
cumulative fluid balance in mililiter
Measured: aproximately 2 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2020
- Study start14 Sep 2020 (estimated)
- Primary completion30 Sep 2020 (estimated)
- Study completion14 Sep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Vasoplegic SyndromeStudies of the same condition, open and under way.
- 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
- Sequential
- Model description
- Randomized, double-blind, single-center, placebo-controlled study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bürgerspital Solothurn
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marcos Delgado, Bürgerspital Solothurn
- Investigators
- Marcos Delgado, MD, Principal investigator, Bürgerspital Solothurn
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04440085
- Sponsor's protocol ID
- RaGuS
- Acronym
- RaGuS
- Status last verified
- Jun 2020
- First submitted
- 13 Jun 2020
- Last updated
- 19 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We have decided for the Trial not to share the participant Information.
Publications
Tchen S, Sullivan JB. Clinical utility of midodrine and methylene blue as catecholamine-sparing agents in intensive care unit patients with shock. J Crit Care. 2020 Jun;57:148-156. doi: 10.1016/j.jcrc.2020.02.011. Epub 2020 Feb 19.
PubMed 32145658Shaefi S, Mittel A, Klick J, Evans A, Ivascu NS, Gutsche J, Augoustides JGT. Vasoplegia After Cardiovascular Procedures-Pathophysiology and Targeted Therapy. J Cardiothorac Vasc Anesth. 2018 Apr;32(2):1013-1022. doi: 10.1053/j.jvca.2017.10.032. Epub 2017 Oct 27.
PubMed 29223724Jans O, Mehlsen J, Kjaersgaard-Andersen P, Husted H, Solgaard S, Josiassen J, Lunn TH, Kehlet H. Oral Midodrine Hydrochloride for Prevention of Orthostatic Hypotension during Early Mobilization after Hip Arthroplasty: A Randomized, Double-blind, Placebo-controlled Trial. Anesthesiology. 2015 Dec;123(6):1292-300. doi: 10.1097/ALN.0000000000000890.
PubMed 26492477Smits M, Lin S, Rahme J, Bailey M, Bellomo R, Hardidge A. Blood Pressure and Early Mobilization After Total Hip and Knee Replacements: A Pilot Study on the Impact of Midodrine Hydrochloride. JB JS Open Access. 2019 May 14;4(2):e0048. doi: 10.2106/JBJS.OA.18.00048. eCollection 2019 Apr-Jun.
PubMed 31334462Levine AR, Meyer MJ, Bittner EA, Berg S, Kalman R, Stanislaus AB, Ryan C, Ball SA, Eikermann M. Oral midodrine treatment accelerates the liberation of intensive care unit patients from intravenous vasopressor infusions. J Crit Care. 2013 Oct;28(5):756-62. doi: 10.1016/j.jcrc.2013.05.021. Epub 2013 Jul 8.
PubMed 23845791Cardenas-Garcia JL, Whitson MR, Healy K, Koenig S, Narasimhan M, Mayo P: Safety of oral midrodrine as a mehtod of weaning from intravenous vasoactive medication in the medical intensive care unit. Chest 2014, 146(4):224A.
Rizvi MS, Nei AM, Gajic O, Mara KC, Barreto EF. Continuation of Newly Initiated Midodrine Therapy After Intensive Care and Hospital Discharge: A Single-Center Retrospective Study. Crit Care Med. 2019 Aug;47(8):e648-e653. doi: 10.1097/CCM.0000000000003814.
PubMed 31107279Whitson MR, Mo E, Nabi T, Healy L, Koenig S, Narasimhan M, Mayo PH. Feasibility, Utility, and Safety of Midodrine During Recovery Phase From Septic Shock. Chest. 2016 Jun;149(6):1380-3. doi: 10.1016/j.chest.2016.02.657. Epub 2016 Mar 4.
PubMed 26953217Anstey MH, Wibrow B, Thevathasan T, Roberts B, Chhangani K, Ng PY, Levine A, DiBiasio A, Sarge T, Eikermann M. Midodrine as adjunctive support for treatment of refractory hypotension in the intensive care unit: a multicenter, randomized, placebo controlled trial (the MIDAS trial). BMC Anesthesiol. 2017 Mar 21;17(1):47. doi: 10.1186/s12871-017-0339-x.
PubMed 28327122
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RANDOMIZED CASE-CONTROLLED TRIAL ASSESSING MIDODRINE (GUTRON®) IN POSTOPERATIVE VASOPLEGIC PATIENTS
- ClinicalTrials.gov ID
- NCT04440085
- Acronym / sponsor ID
- RaGuS / RaGuS
- Conditions
- Vasoplegic Syndrome, Sirs Due to Noninfectious Process Without Organ Dysfunction, Orthostatic Hypotension
- Keywords
- Midodrine, Vasoplegic syndrome, Noradrenaline, SIRS
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Bürgerspital SolothurnUniversity, hospital or other
- Study start
- 14 Sep 2020 (estimated)
- Primary completion
- 30 Sep 2020 (estimated)
- Study completion
- 14 Sep 2021 (estimated)
- First posted
- 19 Jun 2020 (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.
Vasoplegic syndrome is characterized clinically by reduced systemic vascular resistance and normal or increased cardiac output. It is principally observed in cardiovascular and orthopedic interventions and is characterized by a systemic inflammatory response with the inability of the vascular endothelial muscles to contract and a resistance to the action of vasoactive drugs. This event extends the length of stay in the critical care area due to the need of vasoactive drugs.
The investigators aim to assess the standardized application of midodrine in postoperative patients without sepsis and need of vasoactive drugs in order to reduce the length of stay in critical care area and for extension in hospital.
Detailed description
Midodrine is an alpha 1 receptor agonist used usually in cases of hypotension helping to increase blood pressure. The main indication is orthostatic hypotension but there are other clinical conditions where this medicament is often used like hypotension by dialysis, hepatorenal syndrome and after carotid artery stenting.
Vasoplegic syndrome coul be interpreted as a variant of orthostatic hypotension that happens usually after surgical interventions. It produces a loss of systemic vascular resistance due to inflammatory reaction without any signs of infection.
The investigators aim to conduct a randomized, double-blind, single-center, placebo-controlled study of midodrine in patients who present postoperative vasoplegia with no active signs of sepsis but need of vasoactive drugs (Noradrenalin).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Randomized, double-blind, single-center, placebo-controlled study
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Active comparator | Drug: Midodrine HydrochlorideMidodrine will be administered every 8 hours, increasing the dose gradually until a maximum of 30 mg a day is reached. It will be given orally in the following sequence: 2.5 mg - 5 mg - 7.5 mg - 10 mg. The target standard perfusion pressure for all the patients will be a mean arterial pressure (MAP) > 65 mmHg, with unchanged dose of midodrine after target pressure is reached. If the pressure continues to increase, the same sequence will be followed for dose de-escalation. |
| Control group | Placebo comparator | Drug: PlaceboBy placebo group will be followed the same strategy.The target standard perfusion pressure for all the patients will be a mean arterial pressure (MAP) > 65 mmHg, with unchanged dose of placebo after target pressure is reached. If the pressure continues to increase, the same sequence will be followed for dose de-escalation. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Over 18 years of age
- Need of vasoactive drugs after three hours from arrival and adequate volume recovery.
Key exclusion criteria (8 listed)
- Signs of infection (anamnesis or pro-calcitonin > 0.2 with leukocytosis, CRP and/or fever)
- Serum lactate > 2mmol/l
- Mechanical ventilation
- Therapeutic restrictions or comfort measures at arrival
- "de novo" or acute on chronic heart failure (Reduction of known ejection fraction for more than 20 percent, signs of acute lung edema)
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 |
|---|---|---|
| Midodrine HydrochlorideAll patients become standard care resuscitation treatment using liquids and vasoactive drugs in order to get a median arterial pressure ≥ 65 mmHg. Midodrine will be administered according to the evolution of the patient's mean pressure. | Drug | Intervention group |
| PlaceboAll patients become standard care resuscitation treatment using liquids and vasoactive drugs in order to get a median arterial pressure ≥ 65 mmHg. Placebo will be administered according to the evolution of the patient's mean pressure. | Drug | Control group |
Primary outcome
Time
Time frame: aproximately 2 days
Hours from initiation of treatment with midodrine to discharge from critical care area
3 secondary outcomes
Length of stay
Time frame: aproximately 7 days
Vasopresors
Time frame: aproximately 2 days
Fluid balance
Time frame: aproximately 2 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2020.
- Results publication: PubMed 32145658Tchen S, Sullivan JB. Clinical utility of midodrine and methylene blue as catecholamine-sparing agents in intensive care unit patients with shock. J Crit Care. 2020 Jun;57:148-156. doi: 10.1016/j.jcrc.2020.02.011. Epub 2020 Feb 19.
- Results publication: PubMed 29223724Shaefi S, Mittel A, Klick J, Evans A, Ivascu NS, Gutsche J, Augoustides JGT. Vasoplegia After Cardiovascular Procedures-Pathophysiology and Targeted Therapy. J Cardiothorac Vasc Anesth. 2018 Apr;32(2):1013-1022. doi: 10.1053/j.jvca.2017.10.032. Epub 2017 Oct 27.
- Results publication: PubMed 26492477Jans O, Mehlsen J, Kjaersgaard-Andersen P, Husted H, Solgaard S, Josiassen J, Lunn TH, Kehlet H. Oral Midodrine Hydrochloride for Prevention of Orthostatic Hypotension during Early Mobilization after Hip Arthroplasty: A Randomized, Double-blind, Placebo-controlled Trial. Anesthesiology. 2015 Dec;123(6):1292-300. doi: 10.1097/ALN.0000000000000890.
- Results publication: PubMed 31334462Smits M, Lin S, Rahme J, Bailey M, Bellomo R, Hardidge A. Blood Pressure and Early Mobilization After Total Hip and Knee Replacements: A Pilot Study on the Impact of Midodrine Hydrochloride. JB JS Open Access. 2019 May 14;4(2):e0048. doi: 10.2106/JBJS.OA.18.00048. eCollection 2019 Apr-Jun.
- Results publication: PubMed 23845791Levine AR, Meyer MJ, Bittner EA, Berg S, Kalman R, Stanislaus AB, Ryan C, Ball SA, Eikermann M. Oral midodrine treatment accelerates the liberation of intensive care unit patients from intravenous vasopressor infusions. J Crit Care. 2013 Oct;28(5):756-62. doi: 10.1016/j.jcrc.2013.05.021. Epub 2013 Jul 8.
- Results publicationCardenas-Garcia JL, Whitson MR, Healy K, Koenig S, Narasimhan M, Mayo P: Safety of oral midrodrine as a mehtod of weaning from intravenous vasoactive medication in the medical intensive care unit. Chest 2014, 146(4):224A.
- Results publication: PubMed 31107279Rizvi MS, Nei AM, Gajic O, Mara KC, Barreto EF. Continuation of Newly Initiated Midodrine Therapy After Intensive Care and Hospital Discharge: A Single-Center Retrospective Study. Crit Care Med. 2019 Aug;47(8):e648-e653. doi: 10.1097/CCM.0000000000003814.
- Results publication: PubMed 26953217Whitson MR, Mo E, Nabi T, Healy L, Koenig S, Narasimhan M, Mayo PH. Feasibility, Utility, and Safety of Midodrine During Recovery Phase From Septic Shock. Chest. 2016 Jun;149(6):1380-3. doi: 10.1016/j.chest.2016.02.657. Epub 2016 Mar 4.
- Results publication: PubMed 28327122Anstey MH, Wibrow B, Thevathasan T, Roberts B, Chhangani K, Ng PY, Levine A, DiBiasio A, Sarge T, Eikermann M. Midodrine as adjunctive support for treatment of refractory hypotension in the intensive care unit: a multicenter, randomized, placebo controlled trial (the MIDAS trial). BMC Anesthesiol. 2017 Mar 21;17(1):47. doi: 10.1186/s12871-017-0339-x.
- Individual participant dataSharing planned: No. We have decided for the Trial not to share the participant Information.
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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.
Marcos Delgado, MD principal investigator
Bürgerspital Solothurn
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Midodrine Hydrochloride in people with Vasoplegic Syndrome and Sirs Due to Noninfectious Process Without Organ Dysfunction, run by Bürgerspital Solothurn.
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 2 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 19 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marcos Delgado, MD (+4132627 ext. 3820, marcos.delgado@spital.so.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time (time frame: aproximately 2 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 NCT04440085, which also lists 9 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 19 Jun 2020; AzTrials last refreshed its copy on 29 Oct 2026.