Not Yet RecruitingEarly Phase 1ACTRN12624000364572

Terlipressin for the treatment of refractory hypotension in patients otherwise ready for discharge.


Sponsor

Sir Charles Gairdner Hospital

Enrollment

20 participants

Start Date

Apr 1, 2024

Study Type

Interventional

Conditions

Summary

Persistent hypotension in critically ill patients remains a major barrier to discharging patients from the ICU. In patients with adequate tissue perfusion, an agent that could treat hypotension in order to wean continuous intravenous (IV) vasopressors and therefore promote ICU discharge would be useful. The ideal agent would either be a bolus IV agent or an oral agent. There are several possible etiologies of hypotension in the ICU. The most frequent causes include septic shock, vasoplegia from inflammatory conditions, hypovolemia, adrenal insufficiency, and idiosyncratic reactions from medications. For patients whose reversible causes of hypotension have been addressed but still require vasopressors, terlipressin may prove to be a useful adjunctive medication to successfully increase blood pressure. We hypothesize that terlipressin treatment of refractory hypotension in patients otherwise ready for discharge from the ICU shortens duration of receiving IV vasopressors and ICU length of stay (LOS) without increasing hospital length of stay or putting the patient at risk of being readmitted to an ICU.


Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria4

  • Adults (>=18 years of age)
  • Admitted to the SCGH ICU
  • Requiring IV vasopressors (metaraminol, noradrenaline, central or peripheral) for more than 6 hours
  • Rate of less than 10 mcg/min of noradrenaline

Exclusion Criteria10

  • Inadequate tissue oxygenation ((lactate > 2 mmol plus any acute rise in creatinine by at least 50 mmol/l within 24 hours), or acute rise in ALT > 3x)
  • Mesenteric ischaemia or recent laparotomy
  • Hypovolemic shock (uncorrected) or hypotension due to adrenal insufficiency (if a serum cortisol assessment had been performed for clinical reasons
  • Severe organic heart disease (EF < 35%, recent MI or heart failure (last month))
  • Uncontrolled hypertension
  • Conditions that may be exacerbated by fluid overload (chronic renal failure, cardiac disease)
  • Uncorrected hypokalemia (<3) or hypomagnesemia (< 0.6) as may prolong QT interval
  • Hyponatraemia – Na <130
  • Women between the ages of 18-55 who have not had a surgical hysterectomy will only be eligible or for inclusion if they have a negative urine pregnancy test.
  • Pregnancy testing will not need to be repeated if there is a documented negative urine pregnancy test that was obtained within 7 days prior to starting study drug, provided the woman was an ICU inpatient throughout that period of time.

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Interventions

Subjects will be randomized to receive 1mg q6h of terlipressin IV The dose would be given once every 6 hrs until ready for ICU discharge. If there is no change in the noradrenaline dose at 12 hrs, the

Subjects will be randomized to receive 1mg q6h of terlipressin IV The dose would be given once every 6 hrs until ready for ICU discharge. If there is no change in the noradrenaline dose at 12 hrs, the dose of the study drug would be increased to 2mg every 6 hrs until ready for ICU discharge., The adherence to intervention would be monitored by looking at the ICU flow chart which gets updated hourly. The bed side nurse will be educated as well, and the study team will ensure compliance. No blood tests are required. Clear colourless aqueous solution, - 5 mL of injection solution contains 1 mg terlipressin acetate equivalent to 0.85 mg terlipressin. The rationale for using 1 mg is based on the typical dose that is the most commonly used starting dose. ICU standard clinical care will continue for treatment of refractory hypotension requiring IV vasopressor treatment. ICU Standard of care includes bedside monitoring of the blood pressure and achieving/maintaining the mean arterial pressure set by the clinician with or without the use of vasoactive agents.


Locations(1)

Sir Charles Gairdner Hospital - Nedlands

WA, Australia

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ACTRN12624000364572


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