Antidote for Valproic Acid Toxicity: a New Indication for Meropenem Antibiotic.

NCT04671589 | Unknown Phase 4

• 1 other identifier: N2014
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Acute Valproic acid (VPA) toxicity is an emergency condition which may commonly present with central nervous system (CNS) depression(5). In mild poisoning, associated with VPA ingestions of 200 mg/kg, sedation and lethargy commonly occur(6); while in severe VPA poisoning associated with ingestions of 400 mg/kg or more, life threatening events are likely to occur as respiratory depression, metabolic acidosis, encephalopathy, hemodynamic instability, and cerebral edema which may progress to coma and even death -if not treated promptly. Supportive care along with early gastric decontamination using activated charcoal (AC) (which may only be given if patient presented early after ingestion), in addition to intravenous (IV) administration of Levocarnitine (L-Carnitine) and ensuring adequate airway protection are the cornerstone of treatment, but there remains no drug listed as a specific antidote for acute VPA intoxication. Carbapenem antibiotics augment the clearance of VPA through suppressing its enterohepatic recirculation, as they inhibit the acylpeptide hydrolase enzyme responsible for the reabsorption of the hydrolyzed valproate back to VPA active molecule. Taking advantage of this well-established drug-drug interaction between VPA and carbapenems resulting in significant drop of VPA serum concentration during concomitant use, we propose that administration of meropenem (member of carbapenems group) will prove effectiveness in managing VPA toxicity by achieving lower plasma levels of VPA and/or enhanced alertness; compared with standard care.

Conditions

Drug Toxicity

Keywords

Valproic acid toxicity - Meropenem - Antidote

Outcome Measures

Primary Outcomes (1)

• Evaluate serum Valproic acid concentrations among the two study groups.

  Plasma level of valproic acid

  1 year

Secondary Outcomes (1)

• Assess patients level of consciousness according to the Glasgow Coma Scale (GCS) among the placebo and treatment groups. Assess patients level of consciousness according to the Glasgow Coma Scale (GCS) among the placebo and treatment groups.

  1 year

Study Arms (2)

Meropenem

EXPERIMENTAL

Meropenem 1 gram intravenous every 8 hours

Drug: Meropenem Injection

Placebo

PLACEBO COMPARATOR

Placebo intravenous every 8 hours

Drug: Meropenem Injection

Interventions

Meropenem Injection DRUG

Administration Intravenous meropenem 1gram every 8 hours together with standard care; .

Also known as: Supportive care as fluids and securing airway if needed

Meropenem; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with VPA toxicity will be included if aged 18 years or more. The patient himself/herself should provide informed consent; a family member may take place only if there is an altered mentation that may hinder such procedure.

You may not qualify if:

• Patients will be excluded if presenting one hour following VPA ingestion and were administered AC for gastric decontamination, as it may decrease VPA bioavailability.

Sponsors & Collaborators

• Mabaret Al-Asafara Hospitals: lead

Study Sites (1)

Alexandria University hospitals

Alexandria, Egypt

Location

MeSH Terms

Conditions

Drug-Related Side Effects and Adverse Reactions

Interventions

Meropenem; Palliative Care; Fluid Therapy

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services; Drug Therapy

Study Officials

• Nancy M Ahmed, MSc

  Clinical pharmacist

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nancy M Ahmed, MSc

CONTACT

01005607730; dr.nancymohamed@gmail.com

Amr Abdalla, MD

CONTACT

01000106679; amrabdalla1971icu@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical pharmacist

Study Record Dates

• First Submitted: December 9, 2020
• First Posted: December 17, 2020
• Study Start: June 1, 2021
• Primary Completion: June 1, 2022
• Study Completion: December 1, 2022
• Last Updated: December 17, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)