Ketanserin Effects on Peripheral Temperature and Lactate

NCT03646318 | Unknown Phase 4 DMC

• 1 other identifier: WO 17.123 oost
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Critical Illness

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Lactate clearance

  8 hours (after start of the study medication

• hospital length of stay

  6 months after start of study medication

• mortality

  6 months after start of study medication

• ICU length of stay

  6 months after start of study medication

• ICU mortality

  6 months after start of study medication

Study Arms (2)

Ketanserin

EXPERIMENTAL

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.

Drug: Ketanserin

Placebo

PLACEBO COMPARATOR

The placebo is a standard glucose 5% solution.

Other: Placebo

Interventions

Ketanserin DRUG

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

Ketanserin

Placebo OTHER

Glucose 5% solution

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Onze Lieve Vrouwe Gasthuis: lead
• Frisius Medisch Centrum: collaborator

MeSH Terms

Conditions

Critical Illness

Interventions

Ketanserin

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinazolinones; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo medication
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr. P. H. J. van der Voort

Model Details: Randomised controlled trial (blinded)

Study Record Dates

• First Submitted: April 11, 2018
• First Posted: August 24, 2018
• Study Start: September 1, 2018
• Primary Completion: April 1, 2019
• Study Completion: May 1, 2019
• Last Updated: August 24, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share