RaGuS Trial by Postoperative Patients

NCT04440085 | Unknown Phase 4 DMC

• 1 other identifier: RaGuS
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

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

Keywords

Midodrine; Vasoplegic syndrome; Noradrenaline; SIRS

Outcome Measures

Primary Outcomes (1)

• Time

  Hours from initiation of treatment with midodrine to discharge from critical care area

  aproximately 2 days

Secondary Outcomes (3)

• Length of stay

  aproximately 7 days

• Vasopresors

  aproximately 2 days

• Fluid balance

  aproximately 2 days

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

Midodrine Hydrochloride DRUG

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.

Intervention group

Placebo DRUG

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.

Control group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Over 18 years of age
• Need of vasoactive drugs after three hours from arrival and adequate volume recovery.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bürgerspital Solothurn: lead

Related Publications (9)

• 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.

  PMID: 32145658 RESULT

• 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 Oct 27.

  PMID: 29223724 RESULT

• Jans 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.

  PMID: 26492477 RESULT

• 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.18.00048. eCollection 2019 Apr-Jun.

  PMID: 31334462 RESULT

• 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. doi: 10.1016/j.jcrc.2013.05.021. Epub 2013 Jul 8.

  PMID: 23845791 RESULT

• 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.

  RESULT

• 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.

  PMID: 31107279 RESULT

• 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.

  PMID: 26953217 RESULT

• 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 controlled trial (the MIDAS trial). BMC Anesthesiol. 2017 Mar 21;17(1):47. doi: 10.1186/s12871-017-0339-x.

  PMID: 28327122 RESULT

MeSH Terms

Conditions

Vasoplegia; Hypotension, Orthostatic

Interventions

Midodrine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Hypotension

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Study Officials

• Marcos Delgado, MD

  Bürgerspital Solothurn

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marcos Delgado, MD

CONTACT

+4132627; marcos.delgado@spital.so.ch

René Fahrner, MD

CONTACT

+4132627; r.fahrner@web.de

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Randomized, double-blind, single-center, placebo-controlled study

Study Record Dates

• First Submitted: June 13, 2020
• First Posted: June 19, 2020
• Study Start: September 14, 2020
• Primary Completion: September 30, 2020
• Study Completion: September 14, 2021
• Last Updated: June 19, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share