Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19

NCT04365985 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 2020-097
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Ideal new treatments for Novel Coronavirus-19 (COVID-19) would help halt the progression disease in patients with mild disease prior to the need for artificial respiration (ventilators), and also provide a rescue treatment for patients with severe disease, while also being affordable and available in quantities sufficient to treat large numbers of infected people. Low doses of Naltrexone, a drug approved for treating alcoholism and opiate addiction, as well as Ketamine, a drug approved as an anesthetic, may be able to interrupt the inflammation that causes the worst COVID-19 symptoms and prove an effective new treatment. This study will investigate their effectiveness in a randomized, blinded trial versus standard treatment plus placebo.

Conditions

COVID-19; Acute Respiratory Distress Syndrome; Severe Acute Respiratory Syndrome (SARS); Coronavirus Infections

Keywords

naltrexone; ketamine; cytokine storm; Interleukin-2; therapeutic treatment

Outcome Measures

Primary Outcomes (1)

• Progression of Oxygenation Needs

  Count of participants initially presenting with mild/moderate disease who progress to requiring advanced oxygenation (high flow nasal canula, non-rebreather, continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or intubation)

  up to 1 month

Secondary Outcomes (10)

• Renal Failure

  up to 1 month

• Liver Failure

  up to 1 month

• Cytokine Storm

  up to 1 month

• COVID Mortality

  up to 1 month post hospital discharge

• Length of Hospital Stay

  up to 1 month

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo by mouth 1 time per day for patients with stage I or stage 2A COVID-19

Other: Placebo

Naltrexone

EXPERIMENTAL

Naltrexone 4.5 mg by mouth 1 time per day for patients with stage I or stage 2A COVID-19.

Drug: Naltrexone

Ketamine

EXPERIMENTAL

Ketamine IV infusion (0.15 mg/kg based on total body weight for maximum 20 mg every 6 hours) for patients with stage 2B or stage 3 COVID-19; may be increased to 0.3 mg/kg based on total body weight for a maximum of 30 mg every 6 hours if needed. Patients entering this arm from the placebo or naltrexone arms remain on those medications as well.

Drug: Naltrexone; Drug: Ketamine; Other: Placebo

Interventions

Naltrexone DRUG

Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..

Also known as: ReVia, Vivitrol

Ketamine; Naltrexone

Ketamine DRUG

Low dose ketamine hydrochloride given intravenously at a dosage of 0.15 mg/kg body weight for maximum 20 mg every 6 hours, to inpatient participants with advanced oxygenation requirements from either time of admission or time of progression of mild/moderate disease until time participant is stable for discharge, as a rescue treatment. If patient is transferred from the naltrexone or placebo arm, they will continue to receive naltrexone/placebo. Dosage of ketamine may be increased to 0.3 mg/kg body weight, maximum 30 mg every 6 hours, if participant does not respond at the lower dosage. Ketamine can be reduced back to 0.15 mg/kg at the clinical decision of the investigator and when patient has hypertensive emergency, the dose can be held until hypertensive emergency is controlled.

Also known as: Ketalar

Ketamine

Placebo OTHER

Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.

Also known as: sugar pill

Ketamine; Placebo

Eligibility Criteria

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

You may qualify if:

• Positive for COVID -19
• Admitted to Beaumont Hospital - Royal Oak, Michigan
• Age ≥18
• Receiving ≤ 6 liters/minute oxygen by nasal cannula for randomization to either placebo or naloxone arm OR receiving ≥ 6 liters/minute oxygen by nasal cannula or requiring advanced oxygenation for placement in ketamine arm

You may not qualify if:

• Known allergy to naltrexone
• Known allergy to ketamine
• Diagnosis of schizophrenia or psychosis
• Pregnancy based on available medical history, existing labs, or verbal report
• On chronic high dose opioids \> 90mg morphine mg equivalence
• Use of naltrexone or Vivitrol within 90 days

Sponsors & Collaborators

• Corewell Health East: lead

Study Sites (1)

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

MeSH Terms

Conditions

COVID-19; Respiratory Distress Syndrome; Severe Acute Respiratory Syndrome; Coronavirus Infections; Cytokine Release Syndrome

Interventions

Naltrexone; vivitrol; Ketamine; Sugars

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Carbohydrates

Results Point of Contact

• Title: Matthew Sims, MD
• Organization: William Beaumont Hospitals

matthew.sims@beaumont.org

248 551-0027

Study Officials

• Matthew Sims, MD PhD

  Beaumont Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: No other parties blinded
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Infectious Disease Research, Beaumont Health; Professor of Internal Medicine and Foundational Medical Studies, OUWB School of Medicine

Model Details: Prospective, single center, randomized, double blinded study of naltrexone with an open label extension using ketamine as a rescue drug for patients who progress in their disease

Study Record Dates

• First Submitted: April 26, 2020
• First Posted: April 28, 2020
• Study Start: April 29, 2020
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: January 26, 2022
• Results First Posted: January 26, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)