Microcirculation Recruitment Using Albumin 20% and Terlipressin in Septic Patients

NCT ID: NCT05080543

Last Updated: 2021-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-31

Study Completion Date

2022-10-31

Brief Summary

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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

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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.

Conditions

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Septic Shock

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

a randomized controlled and double-blinded
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators

Study Groups

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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)

Group Type ACTIVE_COMPARATOR

Albumin 20% and terlipressin

Intervention Type DRUG

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.

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).

Group Type PLACEBO_COMPARATOR

Albumin 20% and terlipressin

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Microcirculation

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amany Mousa Salama Muhammed

OTHER

Sponsor Role lead

Responsible Party

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Amany Mousa Salama Muhammed

CairoU

Responsibility Role SPONSOR_INVESTIGATOR

Central Contacts

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Amany Mousa Salama, Assistant lecturer

Role: CONTACT

+201004820018

Mohamed Sayed Arafa, Lecturer

Role: CONTACT

+201003752053

Other Identifiers

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Microcirculation septic shock

Identifier Type: -

Identifier Source: org_study_id