Rapid Development and Implementation of a Remote ECG-monitored Prospective Randomized Clinical Trial During a Pandemic: Hydroxychloroquine Prophylaxis in COVID-19 Household Contacts

Covid19 Clinical Trial

Official title:

Rapid Development and Implementation of a Remote ECG-monitored Prospective Randomized Clinical Trial During a Pandemic: Hydroxychloroquine Prophylaxis in COVID-19 Household Contacts

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04652648
• Other study ID #: BM02332
• Status: Completed
• Phase: Phase 4
• Start date: May 27, 2020
• Est. completion date: November 15, 2020

Study information

• Verified date: December 2020
• Source: Bryn Mawr Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

- organizing an entirely no in-person contact clinical trial is feasible during a 22 COVID-19 pandemic 23 - Remote smartphone 6-lead ECG monitoring is possible even in a group unfamiliar 24 with the technology 25 - Hydroxychloroquine used prophylactically at 200 mg BID had no observable 26 cardiotoxicity 27 - Additional study using this technique is warranted to look at reliability and cost-28 effectiveness

Description:

Household members were contacted by telephone and provided consent forms via E-mail electronic signatures. Randomization was 2:1 to HCQ 200 mg BID or observation for 10 days with total follow-up of 14 days. COVID status was determined by home saliva PCR assay on days 1 and 14. Study drug was shipped to participants. Data of daily symptoms and 6-lead ECGs using a smartphone KardiaMobile® 6L application were collected.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: November 15, 2020
• Est. primary completion date: October 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• exposure to a COVID-19-infected individual in the same household within five days of diagnosis;
• age >18 years;
• ability to give informed consent to participate in a clinical study;
• ability to swallow oral medications;
• access to a smartphone

Exclusion Criteria:

• allergy or intolerance to hydroxychloroquine (PlaquenilR);
• weight less than 85 pounds;
• eye disease affecting the retina;
• severe kidney or liver disease;
• G6PD-deficiency;
• porphyria;
• long QTc EKG abnormality or family history of this;
• other major EKG abnormalities;
• taking medications that can affect the QT interval including flecainide, amiodarone, digoxin, procainamide, propafenone, sotalol, quinidine, dofetilide, levofloxacin, ciprofloxacin, azithromycin, erythromycin, amitriptyline, doxepin, desipramine, imipramine, fluoxetine, sertraline, venlafaxine, quetiapine, haloperidol, droperidol, thioridazine, ziprasidone, furosemide, sumatriptan or zolmitriptan, cisapride, arsenic, dolasetron, or methadone;
• current pregnancy;
• current hospitalization;
• symptomatic with fever or cough;
• lack of access to a smartphone

Related Conditions & MeSH terms

• Coronavirus Infection
• Coronavirus Infections
• Covid19
• Hydroxychloroquine
• Prophylaxis
• Severe Acute Respiratory Syndrome
• Transmission

Intervention

Drug:
• Hydroxychloroquine
Randomization was 2:1 to HCQ 200 mg BID or 41 observation for 10 days

Locations

Country	Name	City	State
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Paoli Hospital	Paoli	Pennsylvania
United States	Lankenau Medical Center	Wynnewood	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
Bryn Mawr Hospital	Bryn Mawr Hospital Foundation, Cotswold Foundation, Sharpe-Strumia Research Foundation

Country where clinical trial is conducted

United States, 

References & Publications (15)

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Day M. Covid-19: identifying and isolating asymptomatic people helped eliminate virus in Italian village. BMJ. 2020 Mar 23;368:m1165. doi: 10.1136/bmj.m1165. — View Citation

Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents. 2020 May;55(5):105938. doi: 10.1016/j.ijantimicag.2020.105938. Epub 2020 Mar 12. — View Citation

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30;:. — View Citation

Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, Azman AS, Reich NG, Lessler J. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann Intern Med. 2020 May 5;172(9):577-582. doi: 10.7326/M20-0504. Epub 2020 Mar 10. — View Citation

Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, Li Y, Hu Z, Zhong W, Wang M. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020 Mar 18;6:16. doi: 10.1038/s41421-020-0156-0. eCollection 2020. — View Citation

Marquis-Gravel G, Roe MT, Turakhia MP, Boden W, Temple R, Sharma A, Hirshberg B, Slater P, Craft N, Stockbridge N, McDowell B, Waldstreicher J, Bourla A, Bansilal S, Wong JL, Meunier C, Kassahun H, Coran P, Bataille L, Patrick-Lake B, Hirsch B, Reites J, Mehta R, Muse ED, Chandross KJ, Silverstein JC, Silcox C, Overhage JM, Califf RM, Peterson ED. Technology-Enabled Clinical Trials: Transforming Medical Evidence Generation. Circulation. 2019 Oct 22;140(17):1426-1436. doi: 10.1161/CIRCULATIONAHA.119.040798. Epub 2019 Oct 21. Review. — View Citation

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Rolain JM, Colson P, Raoult D. Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century. Int J Antimicrob Agents. 2007 Oct;30(4):297-308. Epub 2007 Jul 16. Review. — View Citation

Spaccarotella CAM, Polimeni A, Migliarino S, Principe E, Curcio A, Mongiardo A, Sorrentino S, De Rosa S, Indolfi C. Multichannel Electrocardiograms Obtained by a Smartwatch for the Diagnosis of ST-Segment Changes. JAMA Cardiol. 2020 Aug 31. doi: 10.1001/jamacardio.2020.3994. [Epub ahead of print] — View Citation

Turakhia MP, Desai M, Hedlin H, Rajmane A, Talati N, Ferris T, Desai S, Nag D, Patel M, Kowey P, Rumsfeld JS, Russo AM, Hills MT, Granger CB, Mahaffey KW, Perez MV. Rationale and design of a large-scale, app-based study to identify cardiac arrhythmias using a smartwatch: The Apple Heart Study. Am Heart J. 2019 Jan;207:66-75. doi: 10.1016/j.ahj.2018.09.002. Epub 2018 Sep 8. — View Citation

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* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	COVID-19 symptom development with positive PCR test	The primary endpoint was development of COVID-19 symptoms with a positive coronavirus PCR test by Day 14.	within 14 days
Secondary	Positive coronavirus PCR test without symptoms	Development of a positive coronavirus PCR test without symptoms by Day 14	By Day 14 (end of study)
Secondary	Hospital admission for COVID-19	hospital admission for COVID-19 symptoms by Day 14	within 14 days of study entry
Secondary	Death by Day 14	Death due to COVID-19 within 14 days of study entry	within 14 days of study entry
Secondary	HCQ discontinuation or study withdrawal	All-cause discontinuation of study medication or study withdrawal by Day 14	within 14 days of study entry
Secondary	Symptom severity at specified time points	overall symptom severity at Day 7 and Day 14	at Day 7 and at Day 14 from study entry
Secondary	COVID -19 rate at study entry	household attack rate at study entry	Day 1 of study
Secondary	EKG changes during study	documentation of EKG changes such as QTc prolongation on HCQ compared with no drug therapy	Day 1 thru Day 14 of study