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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04353037
Other study ID # 2020-0003
Secondary ID
Status Terminated
Phase Phase 2
First received
Last updated
Start date April 7, 2020
Est. completion date July 11, 2020

Study information

Verified date October 2021
Source UnitedHealth Group
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The proposed hypothesis is that high doses of hydroxychloroquine (HCQ) for at least 2 weeks can be effective antiviral medication both as a treatment in ambulatory patients and prophylaxis/treatment in health care workers because it impairs lysosomal function and reorganizes lipid raft (cholesterol and sphingolipid rich microdomains in the plasma membrane) content in cells, which are both critical determinants of Emerging Viral Disease (EVD) infection. This hypothesis is based on a growing literature linking chloroquine to antiviral activity. It is estimated that enough information exists to launch a clinical trial of hydroxychloroquine for COVID-19.


Description:

Sub-Study 1: COVID-19 patients in self-quarantine. Group 1: Hydroxychloroquine 400 mg bid (two 200 mg tablets taken twice a day; totaling 800 mg per day) for two weeks; Group 2: Placebo 2 pills twice a day for two weeks Sub-Study 2: Asymptomatic health care worker prophylaxis. Group 1: Hydroxychloroquine 600 mg once a day (three 200 mg tablets taken once a day) for up to 2 months; Group 2: Placebo 3 pills once a day for up to 2 months; cross-over from placebo to HCQ 600 mg once a day is allowed upon confirmatory diagnosis for COVID-19. PRIMARY OBJECTIVES: Sub-Study 1 (Patients tested for COVID-19 who meet symptomology and age requirements for eligibility): Rate of hospitalization Sub-Study 2 (Health Care Workers): Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months SECONDARY OBJECTIVES Sub-Study 1: Rate of secondary infection of co-inhabitants, adverse events, and negative for COVID-19 (confirmed by accepted testing methods) at 14 days Sub-Study 2: Number of shifts missed; rate of adverse events, and hospitalization at 2 months


Recruitment information / eligibility

Status Terminated
Enrollment 39
Est. completion date July 11, 2020
Est. primary completion date July 11, 2020
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 75 Years
Eligibility Inclusion Criteria: - Able to give informed consent - Subjects meeting the following criteria by Sub-Study: Sub-Study 1: 50-75 years of age; self-reporting as having a fever within four days prior to time of enrollment; and not requiring hospitalization. Enrolled individuals will undergo testing for COVID-19 and sent home for self-quarantine.Participant must be willing and able to provide informed consent, agree to testing for COVID-19 at time of enrollment to confirm diagnosis and two weeks at the end of treatment. Sub-Study 2: Currently employed as a health care worker. Health care workers are defined as : - Medical Doctor (MD) - Doctor of Osteopathic Medicine (DO) - Nurse Practitioner (NP) - Physician's Assistant (PA) - Registered Nurse (RN) - other members of the medical care team with significant COVID-19 exposure; Health care workers meeting the following criteria: - asymptomatic and presumed negative for COVID-19 (no confirmatory testing conducted); - scheduled for an average of >20 hours per week of clinical care over the next 2 months. Participant must agree to standard clinical guidelines and undergo COVID-19 testing upon the presentation of symptoms indicative of an influenza like illness; if a confirmatory COVID-19 diagnosis is given, participant will be offered to cross-over to HCQ 600 mg qd. - Willing to report compliance with HCQ in the form of a diary and participate in other forms of self-reporting (e.g., symptom tracker and experience log). - Subjects are willing and able to go to designated areas for testing of COVID-19/SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). - Participants must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels. - Participants must have adequate baseline organ function Exclusion Criteria: - Inclusion Criteria - Able to give informed consent - Subjects meeting the following criteria by Sub-Study: Sub-Study 1: 50-75 years of age; self-reporting as having a fever within four days prior to time of enrollment; and not requiring hospitalization. Enrolled individuals will undergo testing for COVID-19 and sent home for self-quarantine. Participant must be willing and able to provide informed consent, agree to testing for COVID-19 at time of enrollment to confirm diagnosis and two weeks at the end of treatment. Sub-Study 2: Currently employed as a health care worker (Medical Doctor, MD; Doctor of Osteopathic Medicine, DO; Nurse Practitioner, NP; Physician's Assistant, PA; and Registered Nurse, RN or other members of the medical care team with significant COVID-19 exposure); asymptomatic and presumed negative for COVID-19 (no confirmatory testing conducted); scheduled for an average of >20 hours per week of clinical care over the next 2 months. Participant must agree to standard clinical guidelines and undergo COVID-19 testing upon the presentation of symptoms indicative of an influenza like illness; if a confirmatory COVID-19 diagnosis is given, participant will be offered to cross-over to HCQ 600 mg qd. - Willing to report compliance with HCQ in the form of a diary and participate in other forms of self-reporting (e.g., symptom tracker and experience log). - Subjects are willing and able to go to designated areas for testing of COVID-19/SARS-CoV-2. - Participant must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels. - Participant must have adequate baseline organ function Exclusion Criteria - Allergy to hydroxychloroquine - Pregnant or lactating or positive pregnancy test during pre-medication examination - Receiving any trial treatment drug for 2019-ncov within 14 days prior to screening evaluation (off label, compassionate use or trial related). - Known retinal disease including but not limited to macular degeneration, retinal vein occlusion, visual field defect, diabetic retinopathy - History of interstitial lung disease or chronic pneumonitis unrelated COVID-19. - Due to risk of disease exacerbation, participants with porphyria or psoriasis are ineligible unless the disease is well-controlled, and they are under the care of a specialist for the disorder who agrees to monitor the Participant for exacerbations. - Participants with serious intercurrent illness that requires active intravenous therapy, intense monitoring, or frequent dose adjustments for medication including but not limited to infectious disease, cancer, autoimmune disease, cardiovascular disease. - Participants who have undergone major abdominal, thoracic, spine or central nervous system (CNS) surgery in the last 2 months, or plan to undergo surgery during study participation. - Participants receiving cytochrome P450 enzyme-inducing anticonvulsant drugs (i.e. phenytoin, carbamazepine, Phenobarbital, primidone or oxcarbazepine) within 4 weeks of the start of the study treatment - Participants currently taking digoxin - History or evidence of increased cardiovascular risk including any of the following: - Left ventricular ejection fraction (LVEF) < institutional lower limit of normal. Baseline echocardiogram is not required. - Current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation - History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to enrollment - Current = Class II congestive heart failure as defined by New York Heart Association. - Deemed unable to participate for medical reasons identified by Co-PI and study staff.

Study Design


Intervention

Drug:
Group 1 HCQ
Enrolled participants randomized in Group 1 receive the HCQ drug
Group 2 Placebo
Enrolled participants randomized in Group 2 will receive a placebo drug

Locations

Country Name City State
United States ProHealth New York New York New York

Sponsors (3)

Lead Sponsor Collaborator
UnitedHealth Group ProHealth Care Associates, University of Pennsylvania Perelman School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (17)

Amaravadi RK, Lippincott-Schwartz J, Yin XM, Weiss WA, Takebe N, Timmer W, DiPaola RS, Lotze MT, White E. Principles and current strategies for targeting autophagy for cancer treatment. Clin Cancer Res. 2011 Feb 15;17(4):654-66. doi: 10.1158/1078-0432.CCR-10-2634. Review. — View Citation

Chu VC, McElroy LJ, Chu V, Bauman BE, Whittaker GR. The avian coronavirus infectious bronchitis virus undergoes direct low-pH-dependent fusion activation during entry into host cells. J Virol. 2006 Apr;80(7):3180-8. — View Citation

de Wilde AH, Jochmans D, Posthuma CC, Zevenhoven-Dobbe JC, van Nieuwkoop S, Bestebroer TM, van den Hoogen BG, Neyts J, Snijder EJ. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother. 2014 Aug;58(8):4875-84. doi: 10.1128/AAC.03011-14. Epub 2014 May 19. — View Citation

Keyaerts E, Li S, Vijgen L, Rysman E, Verbeeck J, Van Ranst M, Maes P. Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrob Agents Chemother. 2009 Aug;53(8):3416-21. doi: 10.1128/AAC.01509-08. Epub 2009 Jun 8. — View Citation

Li F. Receptor recognition mechanisms of coronaviruses: a decade of structural studies. J Virol. 2015 Feb;89(4):1954-64. doi: 10.1128/JVI.02615-14. Epub 2014 Nov 26. Review. — View Citation

Liu J, Liao X, Qian S, Yuan J, Wang F, Liu Y, Wang Z, Wang FS, Liu L, Zhang Z. Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, Shenzhen, China, 2020. Emerg Infect Dis. 2020 Jun;26(6):1320-1323. doi: 10.3201/eid2606.200239. Epub 2020 Jun 17. — View Citation

Ong SWX, Tan YK, Chia PY, Lee TH, Ng OT, Wong MSY, Marimuthu K. Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From a Symptomatic Patient. JAMA. 2020 Apr 28;323(16):1610-1612. doi: 10.1001/jama.2020.3227. — View Citation

Rangwala R, Chang YC, Hu J, Algazy KM, Evans TL, Fecher LA, Schuchter LM, Torigian DA, Panosian JT, Troxel AB, Tan KS, Heitjan DF, DeMichele AM, Vaughn DJ, Redlinger M, Alavi A, Kaiser J, Pontiggia L, Davis LE, O'Dwyer PJ, Amaravadi RK. Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma. Autophagy. 2014 Aug;10(8):1391-402. doi: 10.4161/auto.29119. Epub 2014 May 20. — View Citation

Rangwala R, Leone R, Chang YC, Fecher LA, Schuchter LM, Kramer A, Tan KS, Heitjan DF, Rodgers G, Gallagher M, Piao S, Troxel AB, Evans TL, DeMichele AM, Nathanson KL, O'Dwyer PJ, Kaiser J, Pontiggia L, Davis LE, Amaravadi RK. Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma. Autophagy. 2014 Aug;10(8):1369-79. doi: 10.4161/auto.29118. Epub 2014 May 20. — View Citation

Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-848. doi: 10.1007/s00134-020-05991-x. Epub 2020 Mar 3. Erratum in: Intensive Care Med. 2020 Apr 6;:. — View Citation

Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, Seidah NG, Nichol ST. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005 Aug 22;2:69. — View Citation

Vogl DT, Stadtmauer EA, Tan KS, Heitjan DF, Davis LE, Pontiggia L, Rangwala R, Piao S, Chang YC, Scott EC, Paul TM, Nichols CW, Porter DL, Kaplan J, Mallon G, Bradner JE, Amaravadi RK. Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma. Autophagy. 2014 Aug;10(8):1380-90. doi: 10.4161/auto.29264. Epub 2014 May 20. — View Citation

Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585. Erratum in: JAMA. 2021 Mar 16;325(11):1113. — View Citation

Wang H, Yang P, Liu K, Guo F, Zhang Y, Zhang G, Jiang C. SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway. Cell Res. 2008 Feb;18(2):290-301. doi: 10.1038/cr.2008.15. — View Citation

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271. doi: 10.1038/s41422-020-0282-0. Epub 2020 Feb 4. — View Citation

Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. — View Citation

Zheng Y, Shang J, Yang Y, Liu C, Wan Y, Geng Q, Wang M, Baric R, Li F. Lysosomal Proteases Are a Determinant of Coronavirus Tropism. J Virol. 2018 Nov 27;92(24). pii: e01504-18. doi: 10.1128/JVI.01504-18. Print 2018 Dec 15. — View Citation

* Note: There are 17 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Substudy 1 - Number of COVID-19+ PCR Patients in Self-quarantine Who Are Hospitalized Number of COVID-19+ PCR patients in self-quarantine who are hospitalized up to 31 days after beginning HCQ or Placebo Until completion of study, 29 to 31 days after beginning treatment.
Primary Sub Study 2:Number of Health Care Workers Testing Positive at 2 Months Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months Until completion of study, 2 months after start of treatment.
Secondary Sub Study 1 - Secondary Infection of Co-inhabitants of COVID-19 Positive PCR Patients in Self-quarantine Co-inhabitants of COVID-19 positive PCR patients in self-quarantine that test positive up to 31 days after patient begins treatment with HCQ or Placebo Until completion of study, 29 to 31 days after beginning treatment.
Secondary Sub Study 1 - Rate of Negative Tests at End of Treatment for COVID-19 Positive PCR Patients in Self-quarantine Rate of negative tests at end of treatment for COVID-19 positive PCR patients in self-quarantine 15-17 days after completion of 14 day treatment
Secondary Sub Study 1 - Rate of Negative Tests at End of Treatment for COVID-19 Positive PCR Patients in Self-quarantine Rate of negative tests at end of treatment for COVID-19 positive PCR patients in self-quarantine 1-3 days after completion of 14 day treatment
Secondary Sub Study 2:Health Care Workers:Number of Shifts Missed Any work time missed because the participant experienced COVID-like symptoms during their active 2 month period up to ~60 days after enrollment
Secondary Sub Study 2:Health Care Workers: Assessment of Any Medical Events That Occur During the ~60 Day Active Period Assessment of any medical events that occur during the ~60 day active period that is felt to be related to receipt of HCQ Until completion of study, 2 months (~60 days) after start of treatment.
Secondary Sub Study 2:Health Care Workers:Rate of Hospitalization if the participant gets COVID and has severe symptoms and hospitalized, end point reached if before the end of the 2 month period Until completion of study, 2 months after start of treatment.
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