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Ketanserin Effects on Peripheral Temperature and Lactate (KoPTaL)

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ClinicalTrials.gov Identifier: NCT03646318
Recruitment Status : Unknown
Verified August 2018 by PHJ van der Voort, Onze Lieve Vrouwe Gasthuis.
Recruitment status was:  Not yet recruiting
First Posted : August 24, 2018
Last Update Posted : August 24, 2018
Sponsor:
Collaborator:
Medical Centre Leeuwarden
Information provided by (Responsible Party):
PHJ van der Voort, Onze Lieve Vrouwe Gasthuis

Tracking Information
First Submitted Date  ICMJE April 11, 2018
First Posted Date  ICMJE August 24, 2018
Last Update Posted Date August 24, 2018
Estimated Study Start Date  ICMJE September 1, 2018
Estimated Primary Completion Date April 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 22, 2018)
Delta Temperature [ Time Frame: 8 hours (after start of the study medication) ]
Delta Temperature is calculated from the difference between central (rectal) and peripheral (forefoot) temperature
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2018)
  • Lactate clearance [ Time Frame: 8 hours (after start of the study medication ]
    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
  • hospital length of stay [ Time Frame: 6 months after start of study medication ]
    Length of stay hospital
  • mortality [ Time Frame: 6 months after start of study medication ]
    mortality at hospital discharge
  • ICU length of stay [ Time Frame: 6 months after start of study medication ]
    length of stay in the ICU
  • ICU mortality [ Time Frame: 6 months after start of study medication ]
    mortality at ICU discharge
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketanserin Effects on Peripheral Temperature and Lactate
Official Title  ICMJE Ketanserin Effects on Peripheral Temperature and Lactate (KoPTaL)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomised controlled trial (blinded)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Placebo medication
Primary Purpose: Treatment
Condition  ICMJE Critical Illness
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Ketanserin
    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.
    Intervention: Drug: Ketanserin
  • Placebo Comparator: Placebo
    The placebo is a standard glucose 5% solution.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: August 22, 2018)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2019
Estimated Primary Completion Date April 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03646318
Other Study ID Numbers  ICMJE WO 17.123 oost
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party PHJ van der Voort, Onze Lieve Vrouwe Gasthuis
Study Sponsor  ICMJE Onze Lieve Vrouwe Gasthuis
Collaborators  ICMJE Medical Centre Leeuwarden
Investigators  ICMJE Not Provided
PRS Account Onze Lieve Vrouwe Gasthuis
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP