Government Study: Safety And Efficacy Of Hydroxychloroquine As COVID-19 Prophylaxis For At-Risk Population (SHARP): A Cluster Randomized Controlled Trial (SHARP COVID-19)

ClinicalTrials.gov ^ | 04/10/2020

[SeekAndFind]

Sponsor:

Tan Tock Seng Hospital

Collaborators:

National Center for Infectious Diseases

Singapore Clinical Research Institute

Singapore Eye Research Institute

Saw Swee Hock School of Public Health

Duke-NUS Graduate Medical School

Netherlands: Ministry of Health, Welfare and Sports

Information provided by (Responsible Party):

Tan Tock Seng Hospital

STUDY DESCRIPTION

The Coronavirus Disease 2019 (COVID-19) pandemic has placed tremendous stress on the global economy since its outbreak in December 2019. Currently, with nearly 1.3 million confirmed cases, there is still no effective way to contain the disease. The transmission of COVID-19 occurs via direct (prolonged close interaction, within 2 meters for more than 30 minutes) and indirect (fomites) contacts. Locally, the risk of COVID-19 infection in household contacts of confirmed cases is about 4%. These at-risk individuals are identified through contact tracing and infectious may be preventable using post-exposure-prophylaxis (PEP). However, there has yet to be a single effective, safe, and affordable pharmacological agent with such capabilities.

Hydroxychloroquine (HCQ) is a cheap anti-malarial and immunomodulatory agent which may potentially be used as PEP against COVID-19. HCQ is capable of blocking the invasion and intracellular replication of the virus.

Existing studies have reported efficacy of HCQ in treating COVID-19, with reduced time to clinical recovery and few reports of patients suffering from significant side effects. However, existing studies are largely limited by their small sample sizes. Furthermore, there has yet to be a published trial on HCQ's role in PEP.

This cluster randomized trial will evaluate the safety and efficacy of oral HCQ PEP, taken over for 5 days, in reducing the number of infected household contacts of confirmed COVID-19 patients under home quarantine. Comparison will be made between HCQ PEP (treatment group) and no treatment (control group). Subjects will be followed up over a course of 28 days, with daily symptom monitoring conducted over phone calls. Positive outcomes from this study will provide a means for us to battle the COVID-19 pandemic.

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Study Type :	Interventional  (Clinical Trial)
Estimated Enrollment :	3000 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Prevention
Official Title:	Safety And Efficacy Of Hydroxychloroquine As COVID-19 Prophylaxis For At-Risk Population (SHARP): A Cluster Randomized Controlled Trial
Estimated Study Start Date :	April 2020
Estimated Primary Completion Date :	August 2020
Estimated Study Completion Date :	October 2020

Arms and Interventions

Top of Page Study Description Study Design

Arms and Interventions

Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Hydroxychloroquine post exposure prophylaxis Treatment arm will be given Hydroxychloroquine sulfate. Dose: 800 milligrams (mg) (4 pills of 200mg) as single dose on day 1 followed by 400mg (2 pills of 200mg) single dose on day 2, 3,4, 5. Mode of administration: Oral pills of 200mg of HCQ; has to be given in the form of single daily dose. Supply: The total supply of all the pills (12 pills of 200mg per subject in the study group) will be given to the recruited subject from day 1.	Drug: Hydroxychloroquine Sulfate 200 milligram (mg) Tab Oral tablet of Hydroxychloroquine sulfate
Standard Preventive Measures No intervention. Standard recommended preventive measures by the ministry of health ( MOH), Singapore. under which the subjects under control arm will be following the standard measures recommended by Ministry of Health (temperature monitoring 3 times per day, three times video calls by MOH, no mask, advice to close the lid and flush toilet, hand hygiene)	Drug: Hydroxychloroquine Sulfate 200 milligram (mg) Tab Oral tablet of Hydroxychloroquine sulfate

Outcome Measures

Top of Page Study Description Study Design

Arms and Interventions

Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. positive serology or reverse transcriptase (RT-PCR) for COVID-19 up until day 28. [ Time Frame: Until day 28 ]
   COVID-19 infection
   
   

Eligibility Criteria

Top of Page Study Description Study Design

Arms and Interventions

Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

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Ages Eligible for Study:	18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

1. Aged 21 to 80 years.
2. History of close contact or exposure to positive COVID-19 cases in the same household.
3. Absence of symptoms resembling COVID-19 (e.g., fever and acute respiratory or gastrointestinal symptoms)
4. Able to give informed consent.
5. Able to comply with study procedures and follow-up
6. Singapore citizen, permanent resident or long-term pass-holder.

Exclusion Criteria:

1. Pregnant at time of screening or breastfeeding.
2. Known allergy or hypersensitivity to HCQ or other aminoquinoline compounds.
3. Already on HCQ for different indications (e.g., rheumatological diseases, malaria prophylaxis)
4. Diagnosis of other systemic viral or bacterial infection.
5. Use of systemic immunosuppressant agents within 90 days of enrollment (e.g., corticosteroids and immunomodulatory therapy)
6. History of immunocompromised state.
7. History of psychiatric illness.
8. History of psoriasis or porphyria.
9. History of cardiac disease.
10. Other major comorbidities that contraindicate the use of HCQ: i. Hematologic malignancy, ii. Stage 4-5 chronic kidney disease or end-stage renal failure, iii. history of ventricular arrhythmias, iv. current use of drugs that prolong the QT interval
11. History of severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
12. Bradycardia <50beats/min.
13. Uncorrected hypokalemia or hypomagnesemia.
14. Person diagnosed with COVID-19 infection and if he is living in the same household as index case, only he will be excluded but rest of the members of the household will be included.

Contacts and Locations

Top of Page Study Description Study Design

Arms and Interventions

Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT04342156

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Contact: Rupesh Agrawal, MD	6357100 ext 7726	rupesh_agrawal@ttsh.com.sg

Sponsors and Collaborators

Tan Tock Seng Hospital

National Center for Infectious Diseases

Singapore Clinical Research Institute

Singapore Eye Research Institute

Saw Swee Hock School of Public Health

Duke-NUS Graduate Medical School

Netherlands: Ministry of Health, Welfare and Sports

Investigators

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Principal Investigator:	Rupesh Agrawal, MD	Tan Tock Seng Hospital

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Responsible Party:	Tan Tock Seng Hospital
ClinicalTrials.gov Identifier:	NCT04342156
Other Study ID Numbers:	2020/00402
First Posted:	April 10, 2020    Key Record Dates
Last Update Posted:	April 10, 2020
Last Verified:	April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No
Product Manufactured in and Exported from the U.S.:	No

Keywords provided by Tan Tock Seng Hospital:

Post Exposure Prophylaxis (PEP) Hydroxychloroquine Singapore COVID-19

Additional relevant MeSH terms:

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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

[MuttTheHoople]

Anecdotal™

[SauronOfMordor]

Study won’t complete until October, which makes it not that useful right now.

[Hostage]

I am beginning to see a pattern in these CARES funded clinical trials.

Very few of them are missing a critical study arm, HCQ in combination with Zinc.

Unless the diet is rich in Zinc, these studies will likely show mixed results. That’s a temporary win for the Vaccine Lobby.

Good news is POTUS mentioned HCQ with Zinv at yesterday’s task force press conference.

Good news is POTUS is in contact with Dr. Zev Zelenko via Rudy G.

Chances are when POTUS hears previews of results of these clinical trials, that is paid for by the American people, he’s going to ask his military MDs and others to check it out.

Chances are these studies are going to include the combination arm with Zinc.

[ProtectOurFreedom]

I, for one, won’t be satisfied until all 27 types of clinical trials are completed and the drug proven safe and efficacious beyond a shadow of a doubt. Then the drug has to be tested again with Azithromycin and no zinc then again with Azithromycin AND zinc. Only then will we be able to finally BEGIN answering the questions about safety and efficacy.

1) Clinical Trial
2) Open Clinical Trial
3) Single-Blind Clinical Trial
4) Double-Blind Clinical Trial
5) Triple-Blind Clinical Trial
6) Crossover Clinical Trial
7) N-Of-1 Clinical Trial
8) Explanatory Clinical Trial
9) Unicenter Clinical Trial
10) Multicenter Clinical Trial
11) Parallel Clinical Trial
12) Sequential Clinical Trial
13) Community Trial
14) Classification Of The Types Of Design
15) Pilot Study
16) Descriptive Study
17) Observational Study
18) Experimental Study
19) Cross-Sectional Studies
20) Longitudinal Studies
21) Feasibility Study
22) Crossover Study
23) Analytical Study
24) Prospective Study
25) Retrospective Study
26) Case-Control Study
27) Cohort Study

[McGavin999]

So this is just starting? Why wasn’t it done at the beginning of the outbreak, we would already have the answer.

[SeekAndFind]

RE: Very few of them are missing a critical study arm, HCQ in combination with Zinc.

This study is not about treating Covid-19 patients, it’s about determining whether or not Hydroxychloroquine, which already acts as prophylaxis for Malaria, can likewise act as a prophylaxis (protective) for Covid-19.

In other words, can taking it PROTECT against getting the disease?

Why would they add Zinc into the picture? This is not a treatment study.

[5by5]

Study ranking:
-Scientific reliability
Blinded random controlled trial > Observational study > Anecdotal
-Effectiveness at discovering new therapies
Anecdotal > Observational study > Blinded RCT

[ocrp1982]

Indeed. But, there is already a means to ascertain the prophylactic effectiveness of HCQ.
Dr. Wallace, Rheumatologist, Cedar-Sinai, has more than 2000 Lupus patients under his care. They take HCQ continually. His practice is 35 years old and he has not had a single patient to date come down with the Wuhan Virus.
He wrote a letter to the Head of the FDA detailing this and sent copies to other prominent physicians.
For some reason, likely TDS, the MSM refuses to cover this at all.

[tinyowl]

Don’t forget impeachment trial.

[USFRIENDINVICTORIA]

The drug is being prescribed already. Nothing is lost by having clinical trials. If it weren’t being prescribed, you’d have a point. You don’t.

To put the duration of this trial (5 months until preliminary results) in perspective; consider that the average time for approval of a new drug is 12 years. Twelve years — accelerated to 5 months!

Western medicine cannot be separated from clinical trials. There is an infinite number of molecules or blends of molecules that might be medicinal. Most of them are useless. Many of them are harmful. Only a tiny fraction actually works. That’s why there are clinical trials.

In the case of HCQ — it seems to be working & it should be prescribed to anyone who wants it. However, without trials we don’t know the best dose, we don’t know when to give it, we don’t know how well it performs compared to other drugs — we don’t know a whole lot of things.

Let the trials proceed — there’s no harm in that, and much that might be gained. If conservatives continue to complain about conducting clinical trials, expect the leftists to renew claims that conservatives are anti-science, as they have been with regard to the climate hoax. The difference is — this time they’d be right. If conservatives go all-in for HCQ, and we later discover a problem — that will be the end for Trump. Why take that chance? Why not just be satisfied that the drug is being prescribed, and support the clinical trials?

[hinckley buzzard]

Study of prophylactic use, not treatment. Two very different things.

[ProtectOurFreedom]

Do you think the end of the five month trial will immediately result in FDA approval?

I’ve got 50,000 face masks to sell you.

[SeekAndFind]

That’s what I said in Post #7 above.

[SeekAndFind]

I note also that the sponsor of this study is a SINGAPOREAN HOSPITAL!

[Hostage]

Mechanism of action,

HCQ is not to be taken as a prophylactic. It’s not setup that way.

Zinc, IF IT CAN GET IN THE LUNG CELLS, will stop the SARS-COV-2 virus from replicating (multiplying).

So Zinc as a natural nutrient the body needs, can act as a prophylactic, why?

Because if the virus enters the body, then with Zinc loaded up in the cells, the virus is neutered and flushed out with the cytokine immune response, then eliminated in the urine.

HCQ can cover the ACE2 receptacle in pneumocytes and act as a prophylactic that way but it can’t be used long tern like a vitamin or nutrient, But Zinc is a nutrient. It can be used long term. But still needs a doctor’s care because we can overdose on too much Zinc.

Now how is Zinc pushed into cells?

HCQ.

Read more here:

HYDROXYCHLOROQUINE + ZINC — MECHANISM OF ACTION
(Zev’s Tx Regimen)
http://freerepublic.com/focus/f-chat/3831654/posts

[Pikachu_Dad]

and death within 14 days! They had better speed up their timetable.

[Chauncey Gardiner]

Exactly Hostage. Expect a number of misleading studies of HCQ without Zinc, to marginalize its effectiveness. Have seen a few this week already.

[DUMBGRUNT]

No animal tests?

Clearly fast tracking.

[JohnBovenmyer]

Actually HCQ not only can be used long term as a prophylactic, it is one of the most common such drugs in the world. It's used at 400mg/week OTC in much of the malaria ravaged third world. Lupus/rheumatoid arthritis dosage typically is 200mg or 400mg/DAY. So that prophylactic dose is substantially lower. Thus it not only should be even safer than the relatively well tolerated Lupus/RA dosage; it is backed up by an even larger body of safety data. Literally millions take it. Their data may not be as well organized as American Rheumatologists, but a wide overview shows minimal coronavirus in malarial areas. Nigeria has 220M people, loads of malaria, lots of China trade and so far only 8 corona virus deaths. Equador has a bunch of coronavirus, but it's limited to one big malaria free city. The malarial areas of the country are mostly spared according to reports I've read. India still is only lightly affected with corona virus and is recommending anti-malarial prophylaxis dosing for viral prophylaxis.

In vitro studies suggested HCQ would be useful for prophylaxis of corona virus back in the SARS era. Adding zinc wasn't discussed therein. Multiple mechanisms have been suggested for how HCQ affects the virus. Zinc is needed for one of them. Having more than one mechanism is good (less chance of developing resistance) and not unusual. Probably many people get enough zinc via their diet for the zinc mechanism to work without additional zinc. Severe zinc deficiency is rare and very noticeable (look up acrodermatitis enteropathica). How common milder deficiency—mild enough to avoid symptoms, but enough so the suggested antiviral method wouldn't work—I don't know. As it's cheap and seems safe at the suggested doses it's reasonable to add zinc now. But it would be nice to do some studies, so that we eventually understand whether or not it is really needed. HCQ±Zinc theoretically might work on additional viruses; the better knowledge may prove useful. I wouldn't deny zinc to anyone who wants to add it, but with so much clinical material there ought to be enough zinc agnostics around for an uncoerced trial.