Brazilian Clinical Study: Empirical treatment with Hydroxychloroquine and Azithromycin for suspected cases of COVID-19 followed-up by telemedicine

Prevent Senior Institute, São Paulo, Brazil Clinical Study Result ^ | April 2020 | Rodrigo Barbosa Esper M.D., Ph.D., et. al.

[SeekAndFind]

TITLE: Empirical treatment with Hydroxychloroquine and Azithromycin for suspected cases of COVID-19 followed-up by telemedicine

RESEARCHERS:

Rodrigo Barbosa Esper M.D., Ph.D., Rafael Souza da Silva M.D., Fernando Teiichi Costa Oikawa M.D., Ph.D., Marcelo Machado Castro M.D., Alvaro Razuk-Filho M.D., Ph.D., Pedro Benedito Batista Junior M.D., Sergio Wilhelm Lotze M.D., Cleber Nunes da Rocha M.D., Roberto de Sá Cunha Filho M.D., Saulo Emanuel Barbosa de Oliveira M.D, Philipe Leitão Ribeiro, M.D., Valéria Cristina Vigar Martins M.D., Fernando Silva Braga Bueno M.D., Priscila Ligeiro Gonçalves Esper M.D., Eduardo Fagundes Parrillo M.

Corresponding Author: Rodrigo Barbosa Esper M.D., Ph.D

Avenida Lourenço Marques, n158, São Paulo – Brazil

ZIP CODE: 04547-100

Phone: +55 11 999869306

The Ethics Committee approved study number - CONEP/Plataforma Brasil CAAE: 30586520.9.0000.0008 (Número Parecer:3.968.699)

ClinicalTrials.gov Identifier: NCT04348474

ABSTRACT

Background: Telemedicine can facilitate patient’s assessment with initial flu-like symptoms in the COVID-19 pandemic, moreover it promotes social isolation.

Hydroxychloroquine and azithromycin are associated with reduction in COVID-19 patients' viral load. This study aims to assess whether empirical prescription of hydroxychloroquine and azithromycin for patients with suspected COVID-19 is associated with less need for hospitalization Methods: A telemedicine team evaluated suspected COVID-19 outpatients with flu-like symptoms, if no contraindications were detected, treatment with hydroxychloroquine and azithromycin was prescribed after consent from subjects. Patients were monitored daily by telemedicine appointments.

RESULTS:

Of the 636 symptomatic outpatients, 412 started treatment with hydroxychloroquine and azithromycin and 224 refused medications (control group). Need for hospitalization was 1.9% in the treatment group and 5.4% in the control group (2.8 times greater) and number needed to treat was 28 (NNT = 28).

In those who started treatment before versus after the seventh day of symptoms, the need for hospitalization was 1.17% and 3.2%, respectively.

CONCLUSION:

Empirical treatment with hydroxychloroquine associated with azithromycin for suspected cases of COVID-19 infection reduces the need for hospitalization (p< 0.001).

Funding: this study does not have any type of funding

Keywords: SARS-CoV-2; COVID-19; hydroxychloroquine; azithromycin; telemedicine, pandemic.

FOR THE REST OF THE PAPER -- BACKGROUND, METHODS, CLINICAL OUTCOMES, STATISTICAL ANALYSIS, etc. ( WHICH IS IN PDF FORMAT ), PLEASE CLICK THE LINK OF THIS ARTICLE.

[SeekAndFind]

For those who insist that Zinc should be a major component of any study for it to be successful, this study DID NOT include Zinc.

[PlateOfShrimp]

I’ve heard (maybe it was from you!) that zinc is only needed when there is a deficiency. IIRC, Raoult did not use zinc. Also I asked a doctor on FR about zinc, and she said (in a comment somewhere that I am too lazy to find) that her patients were not given zinc because they had no deficiencies.

[DAC21]

That is a significant P value if I recall my Bio Pharma stats correctly???? Still not a huge population as Dr. Farci would point out.

[Eleutheria5]

Well, we do need one with zinc, to verify or refute the efficacy of the original protocol. Also, the control group were patients who refused the treatment, and a real study should be double-blinded, which raises ethical questions that would put a limit on the study. You can’t double-blind a large group of subjects, if the placebo recipients get deathly ill and die. Following clinical results that far is crossing over to Mangele territory.

[Dave Wright]

The data looks encouraging but I think some research scientists will still object to its reliability. Because the treatment and control groups were not blindly randomized and normalized for age, gender, pre-conditions, etc it might have skewed the data. If the people that refused treatment happened to be more men who were also obese it could distort the endpoint outcomes because of confounding factors.

Not trying to be negative on this but the skeptics will bring these objection up when this is peer reviewed.

[SeekAndFind]

I have some issues with their patient selection criteria. I am not sure that all of them were Covid-19 positive.

Just read the following from the paper:

STUDY POPULATION

Patients enrolled in the study were residents of the city of Sao Paulo, Brazil, after the pandemic was officially declared in this city.

Positive epidemiology for COVID-19 was defined as living in a city with more than 100 confirmed cases of COVID-19. Consecutive outpatients with persistent flu-like symptoms (suspected COVID19 infection), persisting for a period equal to or greater than 2 days, were first evaluated by the telemedicine team or by the emergency department medical doctor.

All physicians had access to medical records of all subjects, such as clinical history, laboratory parameters, images exams and electrocardiograms.

Those who had no immediate need for hospitalization and no contraindications for treatment were invited to participate in the study. Treatment with hydroxychloroquine associated with azithromycin was suggested and prescribed if consented from patient.

The swab laboratory was not mandatory and chest computed tomography was performed according to medical judgment.

Lung injury criteria for COVID-19 were defined as the computed tomography scans with the presence of ground glass opacities in multiple lung lobes with bilateral predominance and peripheral localization (which may evolve to the central region).

Definitions of the severity of lung injury according to tomographic aspects were: Mild (<25% of lung involvement), moderate (25% to 50% of lung involvement) and high (>50% of lung involvement).

All patients were part of the same health care provider, with access to the same network of hospitals, outpatient clinics and diagnostic clinics in the city of São Paulo-Brazil.

In case patients needed to be referred to hospital, they were evaluated, admitted and treated by medical staff advised to follow the standard protocol from the institution.

The main hospitalization admission criteria were:
● Worsening general condition
● Oxygen Saturation < 90%

INCLUSION CRITERIA:

● Patient over 18 years old and flu-like persistent symptoms > 3 days, with a probable diagnosis of COVID-19 and no immediate indication for hospitalization.

EXCLUSION CRITERIA:

● Severe related retinopathy
● Severe liver disease
●Myasthenia Gravis
● Known QT enlargement
● Pregnant
●Severe Renal Failure

---

MY COMMENT: To me, it looks like not all of the patients were actually tested for Covid-19. They were simply ASSUMED to have it based on symptoms. What if they had the Flu or Pneumonia unrelated to Covid-19?

Am I wrong in what I understand?

[Mount Athos]

The last study you posted was of advanced cases.

This one is the opposite, given in the early days of symptoms.

Advanced coronavirus cases have severely depleted zinc levels.
They need supplemental zinc for it to work.
They didn’t give it, it didn’t work.

Those in the early days of treatment don’t.
They have normal levels of zinc still.
This study showed it worked without zinc for early patients.

Likewise, those treated with hcq as prophylactic don’t need supplemental zinc for it to work.

[Grimmy]

MY COMMENT: To me, it looks like not all of the patients were actually tested for Covid-19. They were simply ASSUMED to have it based on symptoms. What if they had the Flu or Pneumonia unrelated to Covid-19?

Am I wrong in what I understand?

**********

Could be you’re correct. And could be that the med package is known to work against a wide variety of virus and bacterial infections.

Known to work.

Already tested to the nth.

And known for decades.

[mistfree]

“The data looks encouraging but I think some research scientists will still object to its reliability. Because the treatment and control groups were not blindly randomized and normalized for age, gender, pre-conditions, etc it might have skewed the data. If the people that refused treatment happened to be more men who were also obese it could distort the endpoint outcomes because of confounding factors.

Not trying to be negative on this but the skeptics will bring these objection up when this is peer reviewed.”

True, BUT, there have been no studies on the other side of the equation, the VA study has been totally refuted.
So, every study says it works and no study says it doesn’t, pretty strong even without a huge n value.

[hawkaw]

I think this study supports what many doctors have been saying. I hope now studies show the same results. And I hope the media would quit trashing Trump over this issue.

[SeekAndFind]

RE: The last study you posted was of advanced cases.

This one is the opposite, given in the early days of symptoms.

_______________________________________________

Well, this is the patient profile that Dr. Zelenko tells us has had the MOST successful outcomes. The intent really is to PREVENT hospitalization so that the burden on our healthcare system ( and all healthcare systems around the world ) will be LESSENED.

In fact, I like this study because the intent is to REPLICATE past successful outcomes instead of probing for where it could fail -— i.e. applying it to patients at the last stages of the disease ( as the VA study did ).

My only concern ( as I posted above ) is the PATIENT PROFILE that they applied the drug combo to. I’m not sure that all of them had Covid-19. They were chosen based on symptoms that were Covid-19 Like. How do we know that they did not have the flu or plain pneumonia?

[xrmusn]

Am I wrong in what I understand?
= = = = = = = = = = =

Be careful....too many people start THINKING like that and the whole plan will blow up in everyone’s face.
Can’t have people thinking not EVERYONE has died from the beerflu these past couple of months...

[freeandfreezing]

To me, it looks like not all of the patients were actually tested for Covid-19.

It appears that they did not have a direct test, but used a population of symptomatic people. If COVID-19 infections were randomly distributed in the groups then the improvement in outcomes would still be valid. If, for example, the people who declined the medication had some kind of increased likelihood to have COVID-19 then the results could be skewed. But absent any evidence that does not seem to be likely.

[ocrp1982]

Zinc is not necessary if a person is not seriously deficient. However, Zinc is a necessary component. HCQ works by providing a pathway into the virus for blood zinc. It is the zinc, once inside the virus that stops viral replication.
So, giving zinc along with the other two components cannot hurt. Not giving it to a patient seriously deficient in Zinc will not be effective or, as effective.

[TChad]

Am I wrong in what I understand?

I think you are correct. I also suspect that Dr. Zelenko's results can be criticized on the same basis. On the other hand, Dr. Raoult tested all his patients for COVID-19, and kept repeating the PCR tests during the period of treatment.

Here's the thing (a little Joe Biden lingo): If your goal is just to save patients, it is reasonable to give possibly-effective, generally safe medications (HCQ+AZ±Zn) to people who appear to have COVID-19, without verifying that diagnosis with a PCR test. If your goal is also to convince physicians that your drug treatment is effective against COVID-19, it would help considerably to have at least an initial positive PCR test.

My guess is that both Dr. Zelenko and these Brazilian docs saved lives.

[Eleutheria5]

It could still be said to test the efficacy of CHQ and Zythromycin against persistent flu-like symptoms. But this is not a definitive study of CHQ protocol’s efficacy against Covid-19 imho fwiw.