RaGuS Trial by Postoperative Patients

Study Overview
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Brief Summary
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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
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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).

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

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

Intervention / Treatment
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* Drug: Midodrine Hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Randomized, double-blind, single-center, placebo-controlled study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention group<br>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. | Drug: Midodrine Hydrochloride<br>* 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.<br>|
| Placebo Comparator: Control group<br>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. | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time | Hours from initiation of treatment with midodrine to discharge from critical care area | aproximately 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of stay | days in critical care area and hospital | aproximately 7 days | 
| Vasopresors | Noradrenalin needed doses | aproximately 2 days | 
| Fluid balance | cumulative fluid balance in mililiter | aproximately 2 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Midodrine, Vasoplegic syndrome, Noradrenaline, SIRS