Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

University of Utah COVID-19 Hydrochloroquine Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04342169
Recruitment Status : Recruiting
First Posted : April 10, 2020
Last Update Posted : April 16, 2020
Sponsor:
Information provided by (Responsible Party):
Adam M. Spivak, MD, University of Utah

Brief Summary:

A novel coronavirus, SARS-CoV-2, is responsible for a rapidly spreading pandemic that has reached 160 countries, infecting over 500,000 individuals and killing more than 24,000 people. SARS-CoV-2 causes an acute and potentially lethal respiratory illness, known as COVID-19, that is threatening to overwhelm health care systems due to a dramatic surge in hospitalized and critically ill patients. Patients hospitalized with COVID-19 typically have been symptomatic for 5-7 days prior to admission, indicating that there is a window during which an effective intervention could significantly alter the course of illness, lessen disease spread, and alleviate the stress on hospital resources.

There is no known treatment for COVID-19, though in vitro and one poorly controlled study have identified a potential antiviral activity for HCQ. The rationale for this clinical trial is to measure the efficacy and safety of hydroxychloroquine for reducing viral load and shedding in adult outpatients with confirmed COVID-19.


Condition or disease Intervention/treatment Phase
Coronavirus Infection Coronavirus Infectious Disease Drug: Hydroxychloroquine Drug: Placebo oral tablet Phase 2

Detailed Description:

Background COVID-19 is pandemic with high mortality among hospitalized patients despite a benign course in the large majority of patients infected. Limited data are available from small outpatient studies and have not shown efficacy in preventing hospitalization. Hydroxychloroquine (HCQ) and chloroquine have antiviral and immune-modulating effects, but there are no data concerning their efficacy in reducing viral load and shedding in outpatients.

Evidence supporting possible efficacy for hydroxychloroquine. In cell models, chloroquine both interferes with terminal glycosylation of the ACE2 receptor (the cell surface receptor by which SARS-CoV2 enters human cells) and increases endosomal pH, which interferes (at least in vitro) with a crucial step in viral replication.1,2 HCQ is 5x more potent than chloroquine in a Vero cell model of SARS-CoV-2 infection. In independent experiments, chloroquine has confirmed in vitro activity against SARS-CoV-2. Additionally, HCQ has in vitro efficacy against SARS-CoV-1. According to news releases, an as-yet-unpublished set of case series in China (N reportedly 120) suggests the possibility of rapid viral clearance and low rates of progression to critical illness. In addition to in vitro anti-viral effects chloroquine and HCQ appear to have immune-modulatory effects, especially via suppression of release of TNF and IL6, especially in macrophages.

Evidence against efficacy for hydroxychloroquine. Chloroquine and HCQ have been promoted as extremely broad anti-infective agents for decades. The reported effects include suppression of fungi, atypical bacteria, and viruses. Other than the effects on ACE2 glycosylation, the mechanisms invoked as evidence for efficacy against SARS-CoV-2 have also been invoked for a wide range of viruses. However, when chloroquine and HCQ have been studied in humans, neither agent has demonstrated consistent efficacy in clinical trials, including in HIV, influenza, hepatitis, and Dengue. In one trial, chloroquine resulted in increased viral replication in Chikungunya virus [Roques et al, Viruses 2018 May 17;10(5)] while in another hydroxychloroquine was associated with increased HIV viral load [Paton et al, JAMA 2012 Jul 25;308(4):353]. Expert opinion advises against HCQ for MERS, another serious coronavirus. An underpowered (n=30) study of HCQ in COVID-19 recently published in China did not demonstrate any clinical benefit [Chen et al, J Zhejiang University, 2020 March 9]. The long history of clinical failure despite in vitro anti-viral activity suggests a low probability of efficacy.

Rationale for Trial There is significant publicity concerning the potential use of HCQ in this pandemic, and many patients are seeking access to this unproven therapy. The ANZICS guidelines emphasize that novel treatments should be administered within clinical trials; the Surviving Sepsis Campaign guidelines (http://bit.ly/SSCCOVID-19) also affirm the lack of evidence to support the clinical use of (hydroxy)chloroquine. WHO guidance (https://apps.who.int/iris/bitstream/handle/10665/331446/WHO-2019-nCoV-clinical-2020.4-eng.pdf) also strongly affirms that "investigational anti-COVID-19 therapeutics should be done under ethically approved, randomized, controlled trials." The evidence thus strongly favors equipoise.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Phase 2, prospective, placebo-controlled, parallel group, randomized trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hydroxychloroquine for Outpatients With Confirmed COVID-19
Estimated Study Start Date : April 14, 2020
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : April 2023


Arm Intervention/treatment
Experimental: HCQ
Participants randomized to the HCQ arm will receive HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days. The drug dose (2.4 gm over 5 days) falls at the lower end of doses proposed in various international trials, but it has proven in vitro efficacy, with a ratio of lung tissue trough concentrations to the EC50 (effective concentration to suppress 50% of viral activity) of >20.
Drug: Hydroxychloroquine
HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days

Placebo Comparator: Placebo
Those randomized to placebo will receive a placebo to be taken on the same schedule.
Drug: Placebo oral tablet
Placebo to be taken on the same schedule as HCQ.




Primary Outcome Measures :
  1. Duration of viral shedding [ Time Frame: Days 1-14 ]

Secondary Outcome Measures :
  1. Duration of COVID-19-attributable symptoms [ Time Frame: Everyday through 6 months ]
  2. Hospitalization [ Time Frame: within 14 days of enrollment ]
  3. Duration of viral shedding [ Time Frame: Days 1-14 and Day 28 ]
  4. Adult household contact viral acquisition [ Time Frame: Days 1-14 and Day 28 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient age ≥18 years, competent to provide consent
  • Within 48 hours of positive nucleic acid test for SARS-CoV-2

Exclusion Criteria:

  • Patient already prescribed chloroquine or hydroxychloroquine
  • Allergy to hydroxychloroquine
  • History of bone marrow or solid organ transplant
  • Known G6PD deficiency
  • Chronic hemodialysis, peritoneal dialysis, continuous renal replacement therapy or Glomerular Filtration Rate < 20ml/min/1.73m2
  • Known liver disease (e.g. Child Pugh score ≥ B or AST>2 times upper limit)
  • Psoriasis
  • Porphyria
  • Known cardiac conduction delay (QTc > 500mSec) or taking any prescription medications known to prolong QT interval
  • Concomitant use of digitalis, flecainide, amiodarone, procainamide, or propafenone
  • Seizure disorder
  • Prisoner
  • Weight < 35kg
  • Inability to follow-up - no cell phone or no address or not Spanish or English speaking
  • Receipt of any experimental treatment for SARS-CoV-2 (off-label, compassionate use, or trial related) within the 30 days prior to the time of the screening evaluation
  • Patient or another member of patient's household has been already enrolled in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04342169


Contacts
Layout table for location contacts
Contact: Christina Pacchia, PhD 8012138735 christina.pacchia@hsc.utah.edu

Locations
Layout table for location information
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84108
Contact: Christina Pacchia, PhD    801-213-8735    christina.pacchia@hsc.utah.edu   
Sponsors and Collaborators
University of Utah
Investigators
Layout table for investigator information
Principal Investigator: Adam Spivak, MD University of Utah
Layout table for additonal information
Responsible Party: Adam M. Spivak, MD, Principal Investigator, University of Utah
ClinicalTrials.gov Identifier: NCT04342169    
Other Study ID Numbers: IRB_00131893
First Posted: April 10, 2020    Key Record Dates
Last Update Posted: April 16, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Adam M. Spivak, MD, University of Utah:
coronavirus
COVID-19
hydrochloroquine
placebo
Additional relevant MeSH terms:
Layout table for MeSH terms
Communicable Diseases
Infection
Coronavirus Infections
Severe Acute Respiratory Syndrome
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Hydroxychloroquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents