Lorazepam for the Analgosedation of Pediatric Patients in Mechanical Ventilation.

NCT04646135 | Unknown Phase 2 DMC

• 2 other identifiers: 1954 / 20192019-003901-93
• Study Type: interventional
• Target: 9
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Analgesia

Keywords

Lorazepam; Intensive Care; Analgosedation; Mechanical Ventilation; Propylene Glycol

Outcome Measures

Primary Outcomes (1)

• Lorazepam Pharmacokinetics (AUC)

  AUC of Lorazepam

  72 hours from enrollment

Secondary Outcomes (21)

• Analgosedative efficacy of Lorazepam

  72 hours from enrollment

• COMFORT-BEHAVIOURAL (COMFORT-B) scale

  72 hours from enrollment

• Dropouts due to any adverse event

  72 hours from enrollment

• Adverse Events (AEs)/ Serious Adverse Events (SAEs) registration at end of study

  72 hours from enrollment

• AEs/SAEs registration at end of follow-up

  6 days from enrollment

Study Arms (3)

Sequence 1

EXPERIMENTAL

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

Drug: Lorazepam 4 mg/ml

Sequence 2

EXPERIMENTAL

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

Drug: Lorazepam 4 mg/ml

Sequence 3

EXPERIMENTAL

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

Drug: Lorazepam 4 mg/ml

Interventions

Lorazepam 4 mg/ml DRUG

Lorazepam will be administered intravenously according to the scheduled sequences.

Sequence 1; Sequence 2; Sequence 3

Eligibility Criteria

• Age: 1 Year - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Bambino Gesù Hospital and Research Institute: lead
• Ministero della Salute, Italy: collaborator
• University College, London: collaborator

MeSH Terms

Conditions

Agnosia

Interventions

Lorazepam

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Marco Marano, MD

  Bambino Gesù Hospital and Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marco Marano, MD

CONTACT

0668592765; marco.marano@opbg.net

Marco Ciabattini, MD

CONTACT

0668593077; marco.ciabattini@opbg.net

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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)

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: November 27, 2020
• Study Start: December 1, 2020
• Primary Completion: July 1, 2021
• Study Completion: December 1, 2021
• Last Updated: November 27, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share