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Ketanserin Effects on Peripheral Temperature and Lactate (KoPTaL)

O

Onze Lieve Vrouwe Gasthuis

Status and phase

Unknown
Phase 4

Conditions

Critical Illness

Treatments

Other: Placebo
Drug: Ketanserin

Study type

Interventional

Funder types

Other

Identifiers

NCT03646318
WO 17.123 oost

Details and patient eligibility

About

A high blood lactate and a high peripheral to central temperature difference (deltaT) are associated with a higher mortality in critically ill patients. Both measures are signs of a reduced microcirculatory bloodflow or vasoconstriction and are associated with shock. It is unknown which medication can best be used to improve deltaT and lactate clearance.

Ketanserin is being used in the intensive care setting for decades to optimize circulatory parameters. Ketanserin is a serotonin type 2-receptor blocker (5-HT2). Blocking the 5-HT2 receptor with ketanserin can attenuate pathological vasoconstriction. In these ways ketanserin can reduce vasoconstriction and can improve the microcirculation. As a consequence, the enhanced blood flow in the skin will increase the peripheral temperature and decrease deltaT. At the same time an increased flow in the microcirculation may lead to a reduction in lactate production.

Objective:

To determine the effects of a continuous ketanserin infusion on peripheral temperature and lactate clearance in critically ill patients with either a high lactate or a high deltaT.

Full description

Rationale:

A high blood lactate and a high peripheral to central temperature difference (deltaT) are associated with a higher mortality in critically ill patients. Both measures are signs of a reduced microcirculatory bloodflow or vasoconstriction and are associated with shock. On the other hand, it has not been shown yet that interventions leading to improvement of this temperature gap reduces mortality or improves any other outcome measurement. Moreover, it is unknown which medication can best be used to improve deltaT and lactate clearance.

Ketanserin is being used in the intensive care setting for decades to optimize circulatory parameters. Ketanserin is a serotonin type 2-receptor blocker (5-HT2). Blocking the 5-HT2 receptor with ketanserin can attenuate pathological vasoconstriction. In these ways ketanserin can reduce vasoconstriction and can improve the microcirculation. As a consequence, the enhanced blood flow in the skin will increase the peripheral temperature and decrease deltaT. At the same time an increased flow in the microcirculation may lead to a reduction in lactate production.

Objective:

To determine the effects of a continuous ketanserin infusion on peripheral temperature and lactate clearance in critically ill patients with either a high lactate or a high deltaT.

Study design:

A multicentre double blind randomized controlled trial.

Study population:

All adult intensive care patients above 17 years old with a deltaT of >6°C with informed consent given by the patient or legal representative.

Intervention (if applicable):

The intervention is a continuous pump driven Ketanserin infusion of 0.75 ug/kg/min for eight hours.

The control group will receive the same volume of glucose 5%.

Main study parameters/endpoints:

Change in DeltaT (measured per hour) Change in lactate (measured per 2 hours)

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

The risks of ketanserin infusion are limited but can be a QTc prolongation and a slight decrease in blood pressure. The study needs an arterial blood sample on inclusion, and after 2, 4, 6 and 8 hours of 1.5 ml each. In addition, a 6 ml blood sample at T=4 and T=8 hours.

Enrollment

120 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • DeltaTemperature greater that 6.0 °C.
  • Age 18 years or older
  • Admitted to the ICU for any reason
  • Signed informed consent from the patient or legal representative

Exclusion criteria

  • Pregnancy
  • No possibility to obtain informed consent
  • QTc above 550 msec,
  • Arrhythmias, including bradycardia defined as a heart rate below 50/min; 2nd and 3rd degree AV block; ventricular tachycardia
  • Blood Potassium level < 3.5 mmol/l
  • Blood Magnesium level <0.5 mmol/l
  • Allergy for ketanserin
  • DeltaT less than 6°C.
  • Patients undergoing therapeutic hypothermia
  • Patients admitted after cardiac arrest
  • Patients admitted after cardiac surgery

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

120 participants in 2 patient groups, including a placebo group

Ketanserin
Experimental group
Description:
Ketanserin is a serotonin type 2-receptor blocker (5-HT2). In normal endothelium, the 5-HT1 effects (vasodilation) are the most prominent \[Dabire 1990\]. In endothelium that is damaged, which is the case in sepsis, the 5HT2 effects (vasoconstriction) surpass the 5-HT1 effects. Blocking the 5-HT2 receptor with ketanserin can attenuate this pathological vasoconstriction. In addition, ketanserin has favourable α1-adrenergic blocking properties in the endothelium (vasodilation) that may further reverse the pathological vasoconstriction. In these ways ketanserin can reduce vasoconstriction and can improve the microcirculation.
Treatment:
Drug: Ketanserin
Placebo
Placebo Comparator group
Description:
The placebo is a standard glucose 5% solution.
Treatment:
Other: Placebo

Trial contacts and locations

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Data sourced from clinicaltrials.gov

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