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Lorazepam for the Analgosedation of Pediatric Patients in Mechanical Ventilation.

NCT ID: NCT04646135

Last Updated: 2020-11-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-31

Study Completion Date

2021-12-31

Brief Summary

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The aim of this study is to better define the pharmacokinetic and pharmacodynamic profile of lorazepam for the analgosedation in pediatric intensive care unit. This will help to better define the dosages and administration modalities (bolus or continue infusion) required to achieve analgosedation with lorazepam in pediatric patients undergoing mechanical ventilation.

Detailed Description

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The prolonged use of certain sedative drugs such as midazolam, whose metabolism is associated with the production of active metabolites, can lead to difficult management of sedative therapy and ventilatory weaning. The active metabolites, whose production is variable, determine in fact a difficulty in establishing a precision therapy, thus making it necessary to identify new molecules for sedation in pediatric intensive care unit (PICU). Lorazepam (LZ) is a benzodiazepine with an intermediate duration of activity, administered by continuous infusion or intermittent bolus, which has the advantages of higher potency compared to other benzodiazepines, a low cost and a metabolism that does not produce active metabolites. However, the presence of propylene glycol (PG), an excipient present in intravenous LZ formulations, although generally well tolerated, is potentially associated with episodes of tissue toxicity due to accumulation phenomena; this may represent a risk in cases where LZ is administered in high doses. This study, based on pharmacokinetic models obtained from data already available in the scientific literature, aims to define the pharmacokinetic and pharmacodynamic characteristics of LZ for the analgosedation of pediatric patients admitted to intensive care and subjected to mechanical ventilation. Preliminary evaluation of sedative efficacy will be carried out through COMFORT-B scale assessment.

Conditions

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Analgesia

Keywords

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Lorazepam Intensive Care Analgosedation Mechanical Ventilation Propylene Glycol

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Arm I:

* Day 1: 6 Boluses at 0.1 mg/kg LZ every 4 hr
* Day 2: 6 Boluses at 0.2 mg/kg LZ every 4 hr
* Day 3: Continuous Infusion at 0.025 mg/kg/hr LZ

Arm II:

* Day 1: 6 Boluses at 0.2 mg/kg LZ every 4 hr
* Day 2: 6 Boluses at 0.1 mg/kg LZ every 4 hr
* Day 3: Continuous Infusion at 0.03 mg/kg/hr LZ

Arm III:

* Day 1: 6 Boluses at 0.3 mg/kg LZ every 4 hr
* Day 2: 6 Boluses at 0.1 mg/kg LZ every 4 hr
* Day 3: Continuous Infusion at 0.025 mg/kg/hr LZ

Patients will be monitored for further 3 days of follow-up, after the end of the administration sequence. In case they would still need to undergo analgosedation, other drugs will be administered (e.g. midazolam, dexmedetomidine).

Patients will also be divided into two age groups - 6 patients: age ≥1 year \<5 years (COHORT 1); 3 patients: age ≥5 years - \<12 years (COHORT 2)
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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Sequence 1

The subjects enrolled in this arm, will undergo the following lorazepam administration scheme:

* Day 1: 6 Boluses at 0.1 mg/kg LZ every 4 hours
* Day 2: 6 Boluses at 0.2 mg/kg LZ every 4 hours
* Day 3: Continuous Infusion at 0.025 mg/kg/hour LZ

Group Type EXPERIMENTAL

Lorazepam 4 mg/ml

Intervention Type DRUG

Lorazepam will be administered intravenously according to the scheduled sequences.

Sequence 2

The subjects enrolled in this arm, will undergo the following lorazepam administration scheme:

* Day 1: 6 Boluses at 0.2 mg/kg LZ every 4 hours
* Day 2: 6 Boluses at 0.1 mg/kg LZ every 4 hours
* Day 3: Continuous Infusion at 0.03 mg/kg/hour LZ

Group Type EXPERIMENTAL

Lorazepam 4 mg/ml

Intervention Type DRUG

Lorazepam will be administered intravenously according to the scheduled sequences.

Sequence 3

The subjects enrolled in this arm, will undergo the following lorazepam administration scheme:

* Day 1: 6 Boluses at 0.3 mg/kg LZ every 4 hours
* Day 2: 6 Boluses at 0.1 mg/kg LZ every 4 hours
* Day 3: Continuous Infusion at 0.025 mg/kg/hour LZ

Group Type EXPERIMENTAL

Lorazepam 4 mg/ml

Intervention Type DRUG

Lorazepam will be administered intravenously according to the scheduled sequences.

Interventions

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Lorazepam 4 mg/ml

Lorazepam will be administered intravenously according to the scheduled sequences.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Informed written consent of the parents or legal representatives of minors according to national law;
* Male and/or female subjects of the following ages: ≥1 year - \<12 years;
* Critical patients who need to undergo mechanical ventilation and hospitalized in PICU;

Exclusion Criteria

* Hospitalization in PICU expected to be less than 48 hours long;
* Altered renal function (eGFR according to Schwartz \< 30 mL/min/1.73 m2 or creatininemia \> 2 vn);
* Altered liver function (bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) \> 2 NU);
* Altered cardiac function (Ejection Fraction \< 50%);
* Need for administration of neuromuscular blocking drugs;
* Concomitant therapy with continuous infusion drugs containing PG;
* Metronidazole therapy in the three months prior to enrollment;
* History of exposure to LZ in the seven days prior to enrollment;
* Participation in other experimental clinical trials;
* Patient undergoing extracorporeal circulation (dialysis, ECMO)
* Known allergic reaction to LZ or its excipients;
* Weight \< 9 kg;
* Known immaturity of the enzymatic system of alcohol dehydrogenase;
* Pregnancy in progress;
* Ingestion of antifreeze;
* Treatment with silver sulfadiazine for wound care;
* Oncological pathology diagnosed or suspected;
* Valproic acid therapy
* Patients undergoing continuous infusion therapy with drugs used for sedation prior to admission to the red area (excluding dexmedetomidine).
Minimum Eligible Age

1 Year

Maximum Eligible Age

11 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ministero della Salute, Italy

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role collaborator

Bambino Gesù Hospital and Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Marco Marano

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Marco Marano, MD

Role: PRINCIPAL_INVESTIGATOR

Bambino Gesù Hospital and Research Institute

Central Contacts

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Marco Marano, MD

Role: CONTACT

Phone: 0668592765

Email: [email protected]

Marco Ciabattini, MD

Role: CONTACT

Phone: 0668593077

Email: [email protected]

Other Identifiers

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2019-003901-93

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1954 / 2019

Identifier Type: -

Identifier Source: org_study_id