Corona Virus Infection Clinical Trial
Official title:
PATCH 2 & 3: (Prevention and Treatment of COVID-19 With Hydroxychloroquine) A Double-blind Placebo Controlled Randomized Trial of Hydroxychloroquine in the Prevention and Treatment of COVID-19
Verified date | October 2021 |
Source | UnitedHealth Group |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
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. |
Country | Name | City | State |
---|---|---|---|
United States | ProHealth New York | New York | New York |
Lead Sponsor | Collaborator |
---|---|
UnitedHealth Group | ProHealth Care Associates, University of Pennsylvania Perelman School of Medicine |
United States,
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 all — Click here to view all references
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. |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04384445 -
Zofin (Organicell Flow) for Patients With COVID-19
|
Phase 1/Phase 2 | |
Completed |
NCT04578210 -
Safety Infusion of NatuRal KillEr celLs or MEmory T Cells as Adoptive Therapy in COVID-19 pnEumonia or Lymphopenia
|
Phase 1/Phase 2 | |
Completed |
NCT05065827 -
Lung Ultrasound Findings in Patients With COVID-19 in a UK ED
|
||
Completed |
NCT04720794 -
A Study To Evaluate The Performance of the Lucira Health All-In-One COVID-19 Test Kit vs Hologic Panther Fusion
|
N/A | |
Enrolling by invitation |
NCT04659486 -
Adolescents With COVID-19/MIS-C at HCFMUSP
|
N/A | |
Completed |
NCT04598620 -
Non-invasive Prognostication of COVID-19 Patients by Use of Biomarkers in Exhaled Breath Condensate
|
||
Completed |
NCT05517941 -
Effect of Active Cycle Breathing Technique Along With Incentive Spirometer on COVID19 Patient
|
N/A | |
Recruiting |
NCT04565782 -
Corona Virus Infection Among Liver Transplant Recipients
|
||
Recruiting |
NCT04480333 -
Safety, Tolerability and Pharmacokinetics of Inhaled Nanoparticle Formulation of Remdesivir (GS-5734) and NA-831
|
Phase 1 | |
Active, not recruiting |
NCT04558476 -
Efficacy of CONvalescent Plasma in Patients With COVID-19 Treated With Mechanical Ventilation
|
Phase 2 | |
Completed |
NCT05639998 -
BBV152/BBV154 Heterologus Prime-Boost Study
|
Phase 2 | |
Completed |
NCT04526769 -
Detecting SARS-CoV-2 in Tears
|
||
Completed |
NCT05736926 -
Anal Fissure Among Survivors of COVID-19 Virus Infection.
|
||
Completed |
NCT04523246 -
Training the Innate Immune System Against SARS-CoV-2 (COVID-19) Using the Shingrix Vaccine in Nursing Home Residents
|
Early Phase 1 | |
Withdrawn |
NCT04386447 -
Phase II RCT to Assess Efficacy of Intravenous Administration of Oxytocin in Patients Affected by COVID-19
|
Phase 2 | |
Recruiting |
NCT04583566 -
Differential Expression of Cytokines, Transcriptome and miRNA in Coronavirus Disease 2019 (COVID-19) Egyptian's Patients
|
||
Completed |
NCT04643678 -
Anakinra in the Management of COVID-19 Infection
|
Phase 2/Phase 3 | |
Recruiting |
NCT04579588 -
Understanding Immunity to the Flu Vaccine in COVID-19 Patients
|
||
Terminated |
NCT03331445 -
Inhaled Gaseous Nitric Oxide (gNO) Antimicrobial Treatment of Difficult Bacterial and Viral Lung (COVID-19) Infections
|
Phase 2 | |
Recruiting |
NCT04573348 -
T Cells Response to SARS COV 2 Peptides
|