RaGuS Trial by Postoperative Patients

Orthostatic Hypotension Clinical Trial

— RaGuS  

Official title:

RANDOMIZED CASE-CONTROLLED TRIAL ASSESSING MIDODRINE (GUTRON®) IN POSTOPERATIVE VASOPLEGIC PATIENTS

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04440085
• Other study ID #: RaGuS
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: September 14, 2020
• Est. completion date: September 14, 2021

Study information

• Verified date: June 2020
• Source: Bürgerspital Solothurn
• Contact: Marcos Delgado, MD
• Phone: +4132627
• Email: marcos.delgado[@]spital.so.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: September 14, 2021
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Over 18 years of age

• Need of vasoactive drugs after three hours from arrival and adequate volume recovery.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Hypotension
• Hypotension, Orthostatic
• Orthostatic Hypotension
• Sirs Due to Noninfectious Process Without Organ Dysfunction
• Vasoplegia
• Vasoplegic Syndrome

Intervention

Drug:
• Midodrine Hydrochloride
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.
• Placebo
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bürgerspital Solothurn

References & Publications (9)

Anstey 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 controlle — View Citation

Cardenas-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.

Jans Ø, Mehlsen J, Kjærsgaard-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-co — View Citation

Levine 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. — View Citation

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. — View Citation

Shaefi 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 — View Citation

Smits 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. — View Citation

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. Review. — View Citation

Whitson 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time	Hours from initiation of treatment with midodrine to discharge from critical care area	aproximately 2 days
Secondary	Length of stay	days in critical care area and hospital	aproximately 7 days
Secondary	Vasopresors	Noradrenalin needed doses	aproximately 2 days
Secondary	Fluid balance	cumulative fluid balance in mililiter	aproximately 2 days