Clinical trial NCT03646318: Ketanserin Effects on Peripheral Temperature and Lactate
Official title: Ketanserin Effects on Peripheral Temperature and Lactate (KoPTaL)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Critical Illness
Lead sponsor: Onze Lieve Vrouwe Gasthuis
Sponsor class: OTHER
Collaborators: name: Frisius Medisch Centrum
First posted: 2018-08-24
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised controlled trial (blinded)
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: Delta Temperature
timeFrame: 8 hours (after start of the study medication)
Secondary outcomes:
measure: Lactate clearance
timeFrame: 8 hours (after start of the study medication
measure: hospital length of stay
timeFrame: 6 months after start of study medication
measure: mortality
timeFrame: 6 months after start of study medication
measure: ICU length of stay
timeFrame: 6 months after start of study medication
measure: ICU mortality
timeFrame: 6 months after start of study medication
Other outcomes:
Locations:
Study officials:
References: