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Microcirculation Recruitment Using Albumin 20% and Terlipressin in Septic Patients

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ClinicalTrials.gov Identifier: NCT05080543
Recruitment Status : Not yet recruiting
First Posted : October 15, 2021
Last Update Posted : October 15, 2021
Sponsor:
Information provided by (Responsible Party):
Amany Mousa Salama Muhammed, Cairo University

Tracking Information
First Submitted Date  ICMJE September 29, 2021
First Posted Date  ICMJE October 15, 2021
Last Update Posted Date October 15, 2021
Estimated Study Start Date  ICMJE October 2021
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 13, 2021)
Mean Flow Index 6hs [ Time Frame: 6 hrs ]
Determination the degree the mean flow index (MFI) 6 hrs after administration albumin and terlipressin in patient with septic shock
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2021)
Mean Flow Index 24hs [ Time Frame: 24 hs ]
Determination the degree the mean flow index (MFI) 24 hrs after administration albumin and terlipressin in patient with septic shock.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Microcirculation Recruitment Using Albumin 20% and Terlipressin in Septic Patients
Official Title  ICMJE Recruitment of Microcirculation Using Albumin 20% and Terlipressin in Patients With Septic Shock: a Randomized Controlled Double-blinded Study.
Brief Summary

The aim of this study is to evaluate the effect of combining HSA 20% and terlipressin on the microcirculation in patients with septic shock using the following;-

  • Microcirculation recruitment by Cytocam-IDF.
  • Cardiac output by LiDCOrapid.
  • Measuring serum lactate level.
Detailed Description

Sepsis is one of the major medical problems and is responsible for high morbidity and mortality. Surviving Sepsis Campaign Guideline 2016 introduced 3-hours and 6-hours bundles in management of septic shock. The 2018 update of the Surviving Sepsis Campaign guidelines introduced the 'Hour-1 Bundle' which recommends treatment with intravenous fluids, measurement of serum lactate concentration as a marker of illness severity, administration of vasopressors, obtaining blood cultures and administering broad-spectrum antibiotics, all within the first hour.

The usual targets for resuscitation of patients with septic shock are the macro-circulatory parameters such as mean arterial blood pressure and heart rate; however, it is believed that restoration of microcirculatory parameters is not sufficient to avoid organ failure unless it was associated with improved microcirculatory perfusion. The loss of coherence between macro- and micro-circulatory parameters increases the need to evaluate the microcirculatory blood flow. So impaired microvascular perfusion is increasingly recognized as a major determinant of tissue hypoxia during sepsis and is a key factor in the pathogenesis of sepsis-induced organ failure.

Fluid resuscitation is recommended to be initiated immediately and completed within the first hour. Guidelines recommend at least a 30-mL/kg bolus of crystalloid fluid as the initial resuscitation. Crystalloid is the fluid of choice for initial resuscitation and subsequent intra-vascular volume replacement in patients with sepsis and septic shock.

Albumin in addition to crystalloids is suggested when patients require a substantial amount of crystalloids. Although the guidelines make no recommendation regarding which concentration of albumin should be used, 5% albumin is most commonly used in patients with hypovolemia to administer as much volume as possible.

In 2016, a study showed that in a rat model of normotensive endotoxemia, the infusion of 4% or 20% Human Serum Albumin "HSA" restored microvascular perfusion in otherwise unresuscitated animals. A more stable microvascular improvement noticed with 20% HSA.

Sepsis is also characterized by an enhanced activation of inflammatory and oxidative stress pathways, which leads to endothelial dysfunction and vascular hyporeactivity.

For its ability to counteract oxidative and nitrosative stress, albumin may represent not only a plasma expander but also an endothelium-modulating agent. In an experimental rodent model of endotoxemia, (HSA) prevented endothelial dysfunction and vascular hyporeactivity.

In patients with septic shock requiring vasopressors, a targeted mean arterial pressure "MAP" of 65 mm Hg within the first hour is recommended. Norepinephrine is the recommended first-line vasopressor in septic shock. If MAP is not maintained at 65 mm Hg or greater with norepinephrine alone or if the norepinephrine dose needs to be decreased, either vasopressin (up to 0.03 unit/minute) or epinephrine can be added to norepinephrine. Although norepinephrine is widely regarded as the first-line vasoactive medication in sepsis, literature continues to debate whether the early addition of vasopressin should be common practice.

Terlipressin is a synthetic analogue of vasopressin which has greater selectivity for the V1 receptor that cause vascular smooth muscle vasoconstriction in response to vasopressin and thus could be associated with fewer side effects than vasopressin.

In 2016 a study showed that terlipressin therapy was associated with good improvement in hemodynamic variables and kidney functions more than adrenaline in patients with refractory septic shock despite adequate fluid resuscitation and the use of norepinephrine.

No data was found on effect of combination of albumin and terlipressin on microcirculation in septic patients.

This study aims to investigate the effect of this combination on microcirculation using Cytocam-IDF (incident dark-field illumination), Braedius.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
a randomized controlled and double-blinded
Masking: Single (Investigator)
Primary Purpose: Treatment
Condition  ICMJE Septic Shock
Intervention  ICMJE Drug: Albumin 20% and terlipressin
Evaluation the effect of adding 20% HSA and terlipressin on microvascular flow index (MFI), flow heterogeneity index, total vessel density (TVD), and perfused vessel density (PVD) in comparison to the standard care in patient with septic shock.
Other Name: Microcirculation
Study Arms  ICMJE
  • Active Comparator: Group AT
    will receive a bolus of albumin (1gm/kg) and terlipressin loading dose of 1 mg over 20 minutes followed by infusion at rate (2 μ g/kg/h)
    Intervention: Drug: Albumin 20% and terlipressin
  • Placebo Comparator: Controlled
    will receive the routine management of septic shock patients as culture-based IV antibiotics, IV fluids and intropic support plus a placebo (as lactated ringer solution in the same infusion rates for blinding).
    Intervention: Drug: Albumin 20% and terlipressin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: October 13, 2021)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2022
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • The presence of septic shock meeting all of the following criteria less than 24 hours:-

    1. Clinically possible or probable or microbiologically confirmed infection taking into account the definitions of the "International Sepsis Forum (ISF)"
    2. Despite adequate volume therapy, vasopressors are required to maintain mean arterial pressure (MAP) ≥ 65 mm Hg.
    3. Serum lactate level > 2 mmol/l (18 mg/dl) despite adequate volume therapy.

Exclusion Criteria:

  • Patients who failed to achieve target MAP despite adequate resuscitation with fluids and maximum dose of noreadrenaline.
  • Acute coronary artery disease or underlying cardiac dysfunction [cardiac index (CI) <2.2 l/min/m 2 ].
  • Severe liver disease (Child-Pugh grade C)
  • Chronic renal failure.
  • Known hypersensitivity to Norepinephrine, terlipressin and human albumin.
  • Those having Raynaud's phenomenon, or a vasospastic diathesis and
  • Other causes of shock e.g.; hemorrhagic hypovolaemia, cardiogenic shock, anaphylactic shock, neurogenic shock.
  • Pregnant patients and lactation.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amany Mousa Salama, Assistant lecturer +201004820018 dr.amany.mousa@gmail.com
Contact: Mohamed Sayed Arafa, Lecturer +201003752053 dr.3arafa1@gmail.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05080543
Other Study ID Numbers  ICMJE Microcirculation septic shock
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Amany Mousa Salama Muhammed, Cairo University
Study Sponsor  ICMJE Amany Mousa Salama Muhammed
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Cairo University
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP