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Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT04513314
Other study ID # 20200851
Secondary ID
Status Withdrawn
Phase Phase 4
First received
Last updated
Start date March 28, 2023
Est. completion date March 28, 2023

Study information

Verified date March 2023
Source University of Miami
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The primary purpose of this research is to determine whether Valproate alone, and in combination with Quetiapine, lowers confusion and agitation in persons with severe Corona Virus Disease (COVID)19 pneumonia during weaning from the breathing machine (ventilator). Though Valproate and Quetiapine are often given to persons with severe confusion with agitation, the purpose of this small research study is specifically for: a) persons infected with COVID 2019 on a ventilator whose agitation is not responding to the usual medications (like dexmedetomidine), and b) to reduce the time persons are treated with dexmedetomidine, which requires continuous close monitoring in an ICU.


Description:

This is a pilot feasibility study involving a randomized, single-blind, controlled comparison scheme examining the efficacy and safety of standard of care (n=10) combined with valproate alone, and in combination with quetiapine (N=10) , in order to reduce the magnitude of agitation associated with COVID 19 delirium as assessed by the RASS scale when weaning from a ventilator, and reduce need for dexmedetomidine as assessed by number of doses of dexmedetomidine administered.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date March 28, 2023
Est. primary completion date March 28, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Signed Informed Consent Form by his or her legal/authorized representative - Age = 18 years at time of signing Informed Consent Form - Ability to comply with the study protocol, in the investigator's judgement - Hospitalized with COVID-19 pneumonia confirmed with World Health Organization (WHO) criteria (including an RNA test of any specimen, e.g. respiratory, blood, urine, stool, other bodily fluid) and evidence by chest X-ray or CT scan - Fraction of inspired oxygen (Fi02) = 0.40 and positive end-expiratory pressure (PEEP) =8 OR Fi02 = 0.50 and PEEP =5 - Fi02 and PEEP = values of previous day - Patient has acceptable spontaneous breathing efforts (may decrease vent rate by 50% for 5 minutes to detect effort.) - No neuromuscular blocking agents or blockade. - RASS score initially at -3 =, rising to 3+ after initial attempt to wean from standard of care sedating medications - Other investigational interventions may be permitted Exclusion Criteria: - Known severe allergic reactions to valproate or quetiapine - History of hepatic encephalopathy or end-stage liver disease (Childs-Pugh class B or worse) - Alcohol, or history of alcohol/substance dependence prior to admission - Hx of dementia - Treatment with an antipsychotic agent in the 30 days before ICU admission - Baseline QT duration corrected (QTc) interval = 500 msecs - Pregnancy - Suspected active bacterial, fungal, viral, or other infection (besides COVID-19) - In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 X upper limit of normal (ULN) detected within 24 hours at screening or at baseline - Absolute neutrophil count (ANC) < 1000/microliter (uL) at screening and baseline - Platelet count < 50,000/uL at screening and baseline - Individuals < 18 (infants, children, teenagers) - Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgement, precludes the patient's safe participation in and completion of the study, e.g. active seizure disorder already receiving treatment with lamotrigine - Informed consent could not be obtained from the legally authorized representative.

Study Design


Intervention

Drug:
Valproate
Valproate sodium (enteral or intravenous) will be administered at a dosage of 10 to 15 mg/kg/day. The dosage may be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day.
Quetiapine
Enteral quetiapine dosing on Day 3: 25 mg to 50 mg twice daily. Increase in increments of 50 mg/day to 100 mg/day divided two on Days 4 and 5 to range of 50-400 mg/day by Day 7. Further adjustments can be made in increments of 25-50 mg twice a day, in intervals of not less than 2 days. Recommended dose range is 150-750 mg/day.
Other:
Standard of Care
Standard of Care is a combination of IV dexmedetomidine (D), midazolam (M), ketamine (K) and propofol (P), at the discretion of treating physician.

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
University of Miami

Outcome

Type Measure Description Time frame Safety issue
Primary Change from baseline RASS score of +3 or greater Richmond Agitation Sedation Scale (RASS) score ranges from +4 (combative) to 0 (alert & calm) to -5 (unarousable). Baseline, Day 7
Secondary Total dose of dexmedetomidine administered Total dose of dexmedetomidine administered will be reported from baseline RASS score of +3 or greater. Day 7
Secondary Incidence of Treatment Emergent Adverse Events Incidence of Treatment Emergent Adverse Events will include:
QTc duration > 470 msecs.
Increase in Liver Function Tests to a Grade 3 or higher using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
Suicidality reported as having a score of moderate or high risk using the Columbia-Suicide Severity Rating Scale Screening (C-SSRS). C-SSRS is a calculated risk assessment tool that scores suicidality from no risk to high risk.
Day 7
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