RaGuS Trial by Postoperative Patients

Bürgerspital Solothurn

Status and phase: Unknown; Phase 4

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

Treatments: Drug: Placebo; Drug: Midodrine Hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT04440085

RaGuS

Details and patient eligibility

About

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.

Full 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).

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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50 participants in 2 patient groups, including a placebo group

Intervention group

Active Comparator group

Description:

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.

Treatment:

Drug: Midodrine Hydrochloride

Control group

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo