AnalgesiaPhase 2NCT04646135
Lorazepam for the Analgosedation of Pediatric Patients in Mechanical Ventilation.
A Phase 2 study testing Lorazepam 4 mg/ml in people with Analgesia, run by Bambino Gesù Hospital and Research Institute.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 year to 11 years
- Conditions the study is for
- Analgesia
- What is being tested?
- Lorazepam 4 mg/ml
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- No sites listed yet
- Study dates
- Dec 2020to Dec 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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;
Who cannot join
- 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;
Show all 19Show fewer
- 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).
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Not for Profit, Monocentric, Open Label Trial of Lorazepam, Randomized to Three Different Sequences of Boli and Continuous Infusion, for Sedation of Children Aged ≥1 and <12 Years Admitted in Intensive Care and Mechanically Ventilated.
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.
Read the detailed description
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
- Analgesia
- Being tested
- Lorazepam 4 mg/ml
- Keywords
- Lorazepam, Intensive Care, Analgosedation, Mechanical Ventilation, Propylene Glycol
- Medical subject headings
- Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lorazepam 4 mg/mlDrug
Lorazepam will be administered intravenously according to the scheduled sequences.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: Lorazepam 4 mg/ml |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lorazepam Pharmacokinetics (AUC)
AUC of Lorazepam
Measured: 72 hours from enrollment
Secondary outcomes (21)
Analgosedative efficacy of Lorazepam
Frequency of responder patients (COMFORT-B scale score between 11 and 22 and alertness score between 2 and 3)
Measured: 72 hours from enrollment
COMFORT-BEHAVIOURAL (COMFORT-B) scale
Median (IQR) of COMFORT-B scale score and alertness score. The COMFORT BEHAVIOURAL (COMFORT-B) SCALE consists of six items: alertness, calmness, respiratory response (for children undergoing mechanical ventilation), body movements, facial tension and muscle tone. Each item goes from 1 to 5, assessing the different intensities. The sum of the six ratings leads to a final score ranging from a minimum of 6 to a maximum of 30. A patient is considered to be under-sedated in case of COMFORT-B scores of 23 or higher, over-sedated in case of COMFORT-B scores of 10 or lower.
Measured: 72 hours from enrollment
Dropouts due to any adverse event
Number of interruptions of the experimental administration sequence due to adverse events
Measured: 72 hours from enrollment
Adverse Events (AEs)/ Serious Adverse Events (SAEs) registration at end of study
Number of AEs / SAEs at the end of the administration of the experimental drug
Measured: 72 hours from enrollment
AEs/SAEs registration at end of follow-up
Number of AEs / SAEs at the end of the follow-up period
Measured: 6 days from enrollment
Vital signs at the end of study (Blood Pressure)
Blood Pressure measurement in mmHg, change from baseline (Median (IQR))
Measured: 72 hours from enrollment
Vital signs at the end of study (Heart Rate)
Heart rate measurement in beats per minute (b.p.m), change from baseline (Median (IQR))
Measured: 72 hours from enrollment
Vital signs at the end of study (Body Temperature)
Body temperature measurement in °C, change from baseline (Median (IQR))
Measured: 72 hours from enrollment
Vital signs at the end of follow-up (Blood Pressure)
Blood Pressure measurement in mmHg, change from baseline (Median (IQR))
Measured: 6 days from enrollment
Vital signs at the end of follow-up (Heart Rate)
Heart rate measurement in beats per minute (b.p.m), change from baseline (Median (IQR))
Measured: 6 days from enrollment
Vital signs at the end of follow-up (Body Temperature)
Body temperature measurement in °C, change from baseline (Median (IQR))
Measured: 6 days from enrollment
Plasma concentrations of Propylene Glycol at the end of study
AUC of PG in mg/L in serum
Measured: 72 hours from enrollment
Osmol gap at the end of study
Osmol gap (detected osmolarity - calculated osmolarity) change from baseline (Median (IQR)
Measured: 72 hours from enrollment
C-Cystatin at the end of study
Plasma levels (AUC) of the early marker of kidney damage (C-Cystatin) changes from baseline
Measured: 72 hours from enrollment
N-GAL at the end of study
Plasma levels (AUC) of the early marker of kidney damage (N-GAL) changes from baseline
Measured: 72 hours from enrollment
Kidney Function at the end of study
Estimated Glomerular Filtration Rate (eGFR) change from baseline (Median (IQR))
Measured: 72 hours from enrollment
Lorazepam Pharmacokinetics (Cmax)
Cmax of Lorazepam
Measured: 72 hours from enrollment
Lorazepam Pharmacokinetics (Tmax)
Tmax of Lorazepam
Measured: 72 hours from enrollment
Lorazepam Pharmacokinetics (Drug Clearance)
Drug clearance (CL)
Measured: 72 hours from enrollment
Lorazepam Pharmacokinetics (Half Life)
Half life (t1/2) of Lorazepam
Measured: 72 hours from enrollment
Lorazepam Pharmacokinetics (Cmin)
Cmin of Lorazepam
Measured: 72 hours from enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2020
- Study startDec 2020 (estimated)
- Primary completionJul 2021 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnalgesiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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)
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bambino Gesù Hospital and Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Ministero della Salute, Italy, University College, London
- Responsible party
- Principal investigator, Marco Marano, Bambino Gesù Hospital and Research Institute
- Investigators
- Marco Marano, MD, Principal investigator, Bambino Gesù Hospital and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04646135
- Sponsor's protocol ID
- 1954 / 2019
- Other IDs
- 2019-003901-93, 2019
- Status last verified
- Nov 2020
- First submitted
- 18 Jun 2020
- Last updated
- 27 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Not for Profit, Monocentric, Open Label Trial of Lorazepam, Randomized to Three Different Sequences of Boli and Continuous Infusion, for Sedation of Children Aged ≥1 and <12 Years Admitted in Intensive Care and Mechanically Ventilated.
- ClinicalTrials.gov ID
- NCT04646135
- Acronym / sponsor ID
- 1954 / 2019
- Conditions
- Analgesia
- Keywords
- Lorazepam, Intensive Care, Analgosedation, Mechanical Ventilation, Propylene Glycol
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Bambino Gesù Hospital and Research InstituteUniversity, hospital or other
- Collaborators
- Ministero della Salute, Italy, University College, London
- Study start
- Dec 2020 (estimated)
- Primary completion
- Jul 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 27 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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)
| Arm | Type | Receives |
|---|---|---|
| Sequence 1 | Experimental | Drug: Lorazepam 4 mg/mlThe 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 |
| Sequence 2 | Experimental | Drug: Lorazepam 4 mg/mlThe 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 |
| Sequence 3 | Experimental | Drug: Lorazepam 4 mg/mlThe 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 |
Who may qualify
- Ages
- 1 year to 11 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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;
Key exclusion criteria (19 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lorazepam 4 mg/mlLorazepam will be administered intravenously according to the scheduled sequences. | Drug | Sequence 1, Sequence 2, Sequence 3 |
Primary outcome
Lorazepam Pharmacokinetics (AUC)
Time frame: 72 hours from enrollment
AUC of Lorazepam
21 secondary outcomes
Analgosedative efficacy of Lorazepam
Time frame: 72 hours from enrollment
COMFORT-BEHAVIOURAL (COMFORT-B) scale
Time frame: 72 hours from enrollment
Dropouts due to any adverse event
Time frame: 72 hours from enrollment
Adverse Events (AEs)/ Serious Adverse Events (SAEs) registration at end of study
Time frame: 72 hours from enrollment
AEs/SAEs registration at end of follow-up
Time frame: 6 days from enrollment
Vital signs at the end of study (Blood Pressure)
Time frame: 72 hours from enrollment
Vital signs at the end of study (Heart Rate)
Time frame: 72 hours from enrollment
Vital signs at the end of study (Body Temperature)
Time frame: 72 hours from enrollment
Vital signs at the end of follow-up (Blood Pressure)
Time frame: 6 days from enrollment
Vital signs at the end of follow-up (Heart Rate)
Time frame: 6 days from enrollment
Vital signs at the end of follow-up (Body Temperature)
Time frame: 6 days from enrollment
Plasma concentrations of Propylene Glycol at the end of study
Time frame: 72 hours from enrollment
Osmol gap at the end of study
Time frame: 72 hours from enrollment
C-Cystatin at the end of study
Time frame: 72 hours from enrollment
N-GAL at the end of study
Time frame: 72 hours from enrollment
Kidney Function at the end of study
Time frame: 72 hours from enrollment
Lorazepam Pharmacokinetics (Cmax)
Time frame: 72 hours from enrollment
Lorazepam Pharmacokinetics (Tmax)
Time frame: 72 hours from enrollment
Lorazepam Pharmacokinetics (Drug Clearance)
Time frame: 72 hours from enrollment
Lorazepam Pharmacokinetics (Half Life)
Time frame: 72 hours from enrollment
Lorazepam Pharmacokinetics (Cmin)
Time frame: 72 hours from enrollment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marco Marano, MD principal investigator
Bambino Gesù Hospital and Research Institute
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lorazepam 4 mg/ml in people with Analgesia, run by Bambino Gesù Hospital and Research Institute.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marco Marano, MD (0668592765 ext. +39, marco.marano@opbg.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lorazepam Pharmacokinetics (AUC) (time frame: 72 hours from enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2020.