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Status unknownNCT04440085RaGuSUpdated Jun 19, 2020

RaGuS Trial by Postoperative Patients

A Phase 4 interventional study of Midodrine Hydrochloride and Placebo in Vasoplegic Syndrome, Sirs Due to Noninfectious Process Without Organ Dysfunction and Orthostatic Hypotension, sponsored by Bürgerspital Solothurn. Status unknown. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2020-06-19.

Sponsored by Bürgerspital Solothurn · Phase 4, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Jun 2020), so the status shown — last known as Not yet recruiting — may be out of date.
Phase
Phase 4
Study type
Interventional
Enrollment
50
Allocation
Randomized
Ages
18 Years to 99 Years
Sex
All
01

Study 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.

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).

02

Conditions studied

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

Keywords

  • Midodrine
  • Vasoplegic syndrome
  • Noradrenaline
  • SIRS
03

Who can participate

Ages eligible
18 Years to 99 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

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

Exclusion criteria

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.
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
50 participants (estimated)

Study arms

  • Active comparator
    Intervention group

    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

  • Placebo comparator
    Control group

    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

  • DrugMidodrine 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.

  • DrugPlacebo

    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.

05

What researchers measure

Primary outcomes

  1. Time

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

    Time frame: aproximately 2 days

Secondary outcomes

  1. Length of stay

    days in critical care area and hospital

    Time frame: aproximately 7 days

  2. Vasopresors

    Noradrenalin needed doses

    Time frame: aproximately 2 days

  3. Fluid balance

    cumulative fluid balance in mililiter

    Time frame: aproximately 2 days

06

Study locations

No study locations are listed for this record.

07

References and documents

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 32145658 ↗
  • 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. PubMed 29223724 ↗
  • 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. PubMed 26492477 ↗
  • 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. PubMed 31334462 ↗
  • 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. PubMed 23845791 ↗
  • 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.
  • 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 31107279 ↗
  • 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. PubMed 26953217 ↗
  • 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. PubMed 28327122 ↗

Individual participant data

Plan to share: No — We have decided for the Trial not to share the participant Information.

08

Registry details

Key details

Study ID
NCT04440085
Lead sponsor
Bürgerspital Solothurn
Responsible party
Marcos Delgado (Principal investigator, Bürgerspital Solothurn) — Principal investigator
First posted
Jun 19, 2020
Start date
Sep 14, 2020 (estimated)
Primary completion
Sep 30, 2020 (estimated)
Completion
Sep 14, 2021 (estimated)
Last update
Jun 19, 2020

Study contacts

Marcos Delgado, MD
Contact
marcos.delgado@spital.so.ch
+4132627 ext. 3820
René Fahrner, MD
Contact
r.fahrner@web.de
+4132627 ext. 3398
Marcos Delgado, MD
principal investigator · Bürgerspital Solothurn

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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