NCT03646318

Ketanserin Effects on Peripheral Temperature and Lactate

Ketanserin Effects on Peripheral Temperature and Lactate (KoPTaL)

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: Onze Lieve Vrouwe Gasthuis · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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.

Conditions

• Critical Illness

Interventions

Type	Name	Description
DRUG	Ketanserin	The dose of 0.75 ug/kg/min is a dose that has been used frequently in critically ill patients. The concentration of the study drug infusion will be 40 mg/40 ml glucose 5%. The maximum dose however will be 4.5 mg per hour for patients with a weight more than 100 kg. The pre-filled 50 ml syringes will be filled with 40 ml of a solution containing 40 mg ketanserin or 0 mg ketanserin in glucose 5%. The minimum number of ketanserin vials (2 ml with 5 mg/ml) that are needed is 240 (40 mg = 4 vials per patient). Duration of intervention: 8 hours
OTHER	Placebo	Glucose 5% solution

Timeline

• Start date: 2018-09-01
• Primary completion: 2019-04-01
• Completion: 2019-05-01
• First posted: 2018-08-24
• Last updated: 2018-08-24