Ketanserin Effects on Peripheral Temperature and Lactate

Critical Illness Clinical Trial

— KoPTaL  

Official title:

Ketanserin Effects on Peripheral Temperature and Lactate (KoPTaL)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03646318
• Other study ID #: WO 17.123 oost
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: September 1, 2018
• Est. completion date: May 1, 2019

Study information

• Verified date: August 2018
• Source: Onze Lieve Vrouwe Gasthuis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: May 1, 2019
• Est. primary completion date: April 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Onze Lieve Vrouwe Gasthuis	Medical Centre Leeuwarden

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Delta Temperature	Delta Temperature is calculated from the difference between central (rectal) and peripheral (forefoot) temperature	8 hours (after start of the study medication)
Secondary	Lactate clearance	Lactate clearance is defined as :(Lactate (admission) - Lactate (8 hours))*100 / Lactate (admission) (Lactate (admission) - Lactate (8 hours))*100 / Lactate (admission) A lactate clearance of 10% or more is regarded as clinical relevant	8 hours (after start of the study medication
Secondary	hospital length of stay	Length of stay hospital	6 months after start of study medication
Secondary	mortality	mortality at hospital discharge	6 months after start of study medication
Secondary	ICU length of stay	length of stay in the ICU	6 months after start of study medication
Secondary	ICU mortality	mortality at ICU discharge	6 months after start of study medication