Donald Trump insists hydroxychloroquine ‘works’ after Twitter deleted video saying it’s a COVID cure, backs doctor who blames witchcraft and ‘sex with demons’ for illness and then walks out of his briefing mid-question (Daily Mail)
The president was being pressed by claims Immanuel has made that include face masks not working in combating COVID, alien DNA being used in prescriptions, and that the medical community is trying to make a vaccine to make a person immune to religion.
Trump ended the matter by saying ‘thank you very much’ and leaving the podium.
Immanuel demanded the social media platforms reupload her videos after they were taken down for spreading disinformation. She claimed God would crash their computers if they did not repost her speech.
‘Hello Facebook put back my profile page and videos up or your computers with start crashing till you do. You are not bigger that God. I promise you. If my page is not back up face book will be down in Jesus name,’ Immanuel said in a mistake-littered tweet Monday night.
WHY STUDIES DON’T BACK HYDROXY
Scores of large, credible controlled studies including the 1,542-patient RECOVERY study in the UK and an NIH study, have found the drug offered no benefit, compared to patients who were only given supportive care, like oxygen.
On the heels of the RECOVERY study, the WHO cancelled the hydroxychloroquine arm of its international SOLIDARITY trial of multiple potential coronavirus treatments on June 17.
It came just days after the FDA revoked its emergency use authorization for the use of hydroxychloroquine to treat COVID-19. The agency had also previously posted a warning that the drug may cause dangerous heart arrhythmias.
On July 2, researchers from Henry Ford Health System published a study on hydroxychloroquine to treat coronavirus that caught the White House’s eye.
The study’s main finding was that death rates were 50 percent lower among patients who were treated with the controversial malaria drug. But the Detroit study was done in a manner far flung from the FDA’s ‘gold standard’ for conclusive research.
Research to determine whether a drug works is typically done as what’s called a randomized controlled trial. In this type of study, patients are assigned to either get the drug being tested, or a placebo. Neither doctors nor patients know who got which until the study ends.
The Detroit study was neither randomized, nor controlled.
It was observational, meaning researchers simply compared data on 2,541 COVID-19 patients who got all manner of treatments.
These types of studies are usually used to decide which drugs should undergo ‘gold standard’ testing, not which ones should be the gold standard of treatment.
In the simplest sense, those who got hydroxychloroquine were less likely to die – but they were also more likely to receive steroids, drugs which many studies suggest do work to combat the inflammation that kills many coronavirus sufferers.
While Immanuel has been embraced by Trump and his supporters, the pediatrician and religious minister has made some outlandish claims in the past.
She has often alleged that gynecological problems, like cysts and endometriosis, are actually caused by people dreaming about having intercourse with demons and witches.
Immanuel also claims scientists are working on a vaccine to prevent people from being born religious and asserts that alien DNA is used in modern-day medical treatments.
Donald Trump Jr. called Immanuel’s viral Friday speech a ‘must watch’ and posted a link on his Twitter page, causing his account access to be limited by Twitter for violating its rules.
VT has discovered that Trump has been using an advisory group sent to him by Tea Party Patriots who, from the beginning, advised him COVID 19 was a hoax and that is responsible for every disastrous policy. Trump’s new belief, based on advice from Dr. Stella Immanuel, is that most of America’s problems are caused by demonic sperm.
We at VT are NOT making this up.
The President of the United States thinks the alien DNA, demon sperm doctor is a more authoritative source on hydroxychloroquine than Dr. Fauci. Lord help us.— Amanda Carpenter (@amandacarpenter) July 28, 2020
‼️ Stella Immanuel, Trump’s New COVID-19 Doctor, Believes in Alien DNA, Demon Sperm, and Hydroxychloroquine https://t.co/mGqJXPQnSD— Katie Phang (@KatiePhang) July 28, 2020
Twitter REMOVES TWEET highlighted by Trump falsely claiming COVID 'cure'— Michael O'Grady (@mog7546) July 28, 2020
Trump retweeted the tweet from an account with the handle “@stella_immanuel” that said, "Covid has cure. America wake up"#MOG https://t.co/cJDLJMkoJy via @nbcnews
Trump has personally backed Stella Immanuel and her teachings which include:
- Homosexuality is caused by demonic possession
- Gynecological problems are caused by having sex while dreaming
- Hydroxychloroquine cures COVID 19
- Trump is assailed by witches
Trump and his allies have embraced @stella_immanuel, a doctor with a viral video saying masks aren't needed. But Immanuel has also claimed that some medical issues are caused by sex with demons and witches, and that alien DNA is used in medical treatment. https://t.co/snJwwvtTuc— Will Sommer (@willsommer) July 28, 2020
In addition to her medical practice, Immanuel runs Fire Power Deliverance Ministries, which promises “deliverance from family line witchcraft.”— Who Will Enforce the Law? (@AmericnXX) July 28, 2020
Dr. Stella Immanuel — Who Claims to Fight Witchcraft — Says Hydroxychloroquine Can Cure and Prevent COVID-19 https://t.co/4rGsrQQbXa
Dr. Immanuel's claim that hydroxychloroquine works against coronavirus has gone viral on the right. But Trump supporters haven't noticed so far that Immanuel also believes that some gynecological problems are caused by demonic sperm. https://t.co/ZzLp4KPcCr pic.twitter.com/NlbHGgUVRF— Will Sommer (@willsommer) July 28, 2020
Presidential Advisor Dr. Stella Emmanuel is Nigerian born MD and certified specialist in fighting witches and in interpreting dreams.
Dr Stella Immanuel's Pentecostal ministry trains end time warriors.— Trump For Prison 2020 (@Resist_N0W) July 28, 2020
End Time Warriors? I don't even want to know. pic.twitter.com/ZmQszsEqsY
Trump, a man who has been ‘over the edge’ for some time, today backed a ‘medical group’ claiming witchcraft has been used to destroy his presidency and that Hydroxychlorquine is being plotted against, not as a cure for COVID but rather for ‘evil spells.”
In addition to her medical practice, Immanuel runs Fire Power Deliverance Ministries, which promises “deliverance from family line witchcraft.”— Who Will Enforce the Law? (@AmericnXX) July 28, 2020
Dr. Stella Immanuel — Who Claims to Fight Witchcraft — Says Hydroxychloroquine Can Cure and Prevent COVID-19 https://t.co/4rGsrQQbXa
These are the doctors, witch hunting doctors, that Trump relied on in his “early opening” policy, those that told him COVID 19 was a hoax and, of course we now have 150,000 dead and we know who to blame.
#americasfrontlinedoctors #whitecoatsummit Any possible relationship to this story: https://t.co/v2VQMKTgfV I think so! I’ve researched each Dr at today’s press conference & each (with the exception of 1 or 2 that I couldn’t find much on) have heavy ties to the GOP!— Rose (@RBG11616) July 27, 2020
WOAH!!! Then…. afterwards… Dr. Stella Emmanuel straight up challenged @ChrisCuomo and #AnthonyFauci to give #UrineSamples to prove whether or not her suspicion is correct which is they're currently taking and/or took #Hydroxychloroquine 🦠💊#AmericasFrontlineDoctors pic.twitter.com/4rOwBkIZoC— Jennifer Herbs (@JenniferHerbs) July 28, 2020
The problem is, no one can find who these doctors are or even prove any of them have medical backgrounds at all thou we assume they must as they have been advising the president all along.
We also might ask why Fauci and others, who must know about this group, have never told the American people?
Ah, but it gets better. The website, www.firepowerministry.org, aids Trump supporters in fighting witchcraft, ‘soul hunters’ and it dream interpretation. It is filled with bad spelling and some really crazy shit. Please, go look. Send money if you must. For doubters, the same woman in the featured image is seen below on this screen grab:
Donald Trump just tweeted, retweeted nearly 1 million times, a link to a Breitbart produced video filled with totally fake and extremely dangerous lies about the effectiveness of Hydroxychloroquine (HDC).
Gee, this was really hard to Google who these 'doctors' really are: https://t.co/rWkY0kGvP4— DoOgLe (@PHL_BirdsFlyers) July 28, 2020
Trump and his family have made millions through securing world supplies of this toxic drug that has no effect on COVID 19 even when put in a cocktail of antibiotics. Instead, it kills many patients and leaves others hopelessly brain damaged or with multiple organ failure.
Hydroxychloroquine is trending because this "doctor" is on a video claiming it's a cure for Covid-19.— JackWBower (@Trumpet1984) July 28, 2020
She claims other doctors are lying about it to hurt Trump.
She's with America's Frontline Doctors which must be legit because their website has been around for 11 days now.
The story of how YouTube (Google) along with Twitter and Facebook “saved us from Trump” is below. Note that Google pushed the video as sponsored while it has banned VT stories warning of HDC dangers, stories backed by the FDA, CDC and WHO, but banned anyway.
Of course, Google’s Sergei Brin has always worked for the CIA. VT published that as well, which was, now wait for it, banned by Google.
In April, VT predicted 150,000 COVID deaths at the end of July. That figure was hit on July 28. Jim Dean thinks we should congratulate ourselves for having that and other key truths banned from Google, Facebook and every news outlet in America.
When a single French doctor, backed by no evidence at all, announced that HDC cured covid, Trump jumped on it. The chemicals needed to manufacture massive amounts of HDC were controlled by Israel, who gets rich of Malaria, a really good business.
A deal was cut between Israeli scamsters, Trump and Kushner to buy up all supplies, even those from India, and to push the drug as a cure. By April, HDC was proven to be fatal and had already killed hundreds of aging veterans. The April study, reported ONLY in VT and banned by Google, covered this VA scandal.
Only days ago, the final study, and this is months after HDC was banned by the FDA, CDC and WHO, was published. The abstract of that study is in Appendix I.
Daily Beast: Twitter has pulled a video of doctors making false claims about the novel coronavirus after it was shared by President Trump. Late Monday night, the president stumbled across the viral video which showed fringe doctors touting the controversial anti-malarial drug hydroxychloroquine as “a cure for COVID” and doubting the effectiveness of wearing masks.
The claims made in the video directly contradicted the advice of Trump’s own public health experts—but, despite that, he slammed the retweet button. Now, Trump’s page shows a disclaimer where the retweet once was, reading: “This Tweet is no longer available.”
A Twitter spokesperson told CNN: “We’re taking action in line with our COVID misinfo policy.” Facebook and YouTube have also confirmed they removed the misleading video. Despite what Trump appears to believe, clinical trials have found that hydroxycholroquine has shown no real benefit in treating coronavirus patients, and has potentially deadly side effects.
CNN: In this photo illustration a pack of Hydroxychloroquine Sulfate medication is held up.
(CNN Business)A video featuring a group of doctors making false and dubious claims related to the coronavirus was removed by Facebook, Twitter, and YouTube after going viral online Monday.
Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited.
We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days.
The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed.
A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P=1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P=1.00).
Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent.
Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123. opens in new tab.)
Coronavirus disease 2019 (Covid-19), the disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), is associated with considerable morbidity and mortality.1,2Hydroxychloroquine has antiviral effects in vitro, and, in association with azithromycin, was suggested to decrease SARS-CoV-2 viral load in a small, nonrandomized study.3,4
On the basis of this evidence, hydroxychloroquine plus azithromycin has been used by some practitioners to treat patients with Covid-19. Furthermore, some national regulatory agencies have authorized the use of hydroxychloroquine in hospitalized patients with this disease.5,6
However, observational studies have suggested no beneficial effect of chloroquine or hydroxychloroquine in hospitalized patients with Covid-19.7,8 Previous randomized, controlled trials have shown no benefit of hydroxychloroquine for either postexposure prophylaxis or treatment of Covid-19.9-11
We performed a multicenter, randomized, open-label, controlled trial (Coalition Covid-19 Brazil I) to assess whether hydroxychloroquine, either alone or in combination with azithromycin, would be effective in improving clinical status at 15 days after hospital admission due to mild-to-moderate Covid-19.
TRIAL DESIGN AND OVERSIGHT
We conducted this three-group trial at 55 hospitals in Brazil. The trial was designed by the executive committee (see the Supplementary Appendix, available with the full text of this article at NEJM.org) and approved by the Brazilian National Commission for Research Ethics, the Brazilian Health Regulatory Agency (ANVISA), and ethics committees at the participating sites. The trial was funded by the hospitals and research institutes participating in Coalition Covid-19 Brazil (see the Supplementary Appendix).
EMS Pharma provided additional funding and logistic support for the trial and also donated and supplied the trial drugs. EMS Pharma had no role in the conduct of the trial, the analysis, or the decision to submit the manuscript for publication.
The trial was overseen by an independent international data and safety monitoring committee. The executive committee vouches for the completeness and accuracy of the data and for the fidelity of the trial to the protocol (available at NEJM.org).
The trial included consecutive patients who were 18 years of age or older and who had been hospitalized with suspected or confirmed Covid-19 with 14 or fewer days since symptom onset.
Among the reasons for exclusion from the trial were the use of supplemental oxygen at a rate of more than 4 liters per minute as administered by a nasal cannula or at a level of at least 40% as administered by a Venturi mask; the use of supplemental oxygen administered by a high-flow nasal cannula or invasive or noninvasive ventilation; previous use of chloroquine, hydroxychloroquine, azithromycin, or any other macrolide for more than 24 hours before enrollment (and since the onset of symptoms); and a history of severe ventricular tachycardia or electrocardiographic findings with a corrected QT interval (QTc) of at least 480 msec.
Complete information on the inclusion and exclusion criteria is provided in the Supplementary Appendix. All the patients provided written or electronic informed consent before randomization.
RANDOMIZATION, INTERVENTIONS, AND FOLLOW-UP
Patients were randomly assigned in a 1:1:1 ratio to receive standard care (control group), standard care plus hydroxychloroquine at a dose of 400 mg twice daily for 7 days (hydroxychloroquine-alone group), or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once a day for 7 days.
Randomization was performed in blocks of six and was stratified according to the use or nonuse of supplemental oxygen at the time of randomization. Randomization was performed centrally by means of an electronic case-report form system (RedCap) as described in the Supplementary Appendix.12
The current standard care for Covid-19 was at the discretion of the treating physicians. The use of glucocorticoids, other immunomodulators, antibiotic agents, and antiviral agents was allowed (see the Supplementary Appendix).
The administration of hydroxychloroquine or chloroquine was not allowed in the control group, and the use of macrolides was not allowed in the control group or the hydroxychloroquine-alone group. Guidance was provided to the investigators about how to adjust or interrupt treatment according to side effects and laboratory abnormalities.
Data were collected daily, from randomization until day 15, in the electronic case-report form. For patients who were discharged before day 15, a structured telephone call to the patient or the patient’s family was conducted on or after day 15 by an interviewer who was unaware of the assigned trial group in order to assess vital status and return to routine activities.
The primary outcome was clinical status at 15 days, evaluated with the use of a seven-level ordinal scale. Scores on the scale were defined as follows: a score of 1 indicated not hospitalized with no limitations on activities; 2, not hospitalized but with limitations on activities; 3, hospitalized and not receiving supplemental oxygen; 4, hospitalized and receiving supplemental oxygen; 5, hospitalized and receiving oxygen supplementation administered by a high-flow nasal cannula or noninvasive ventilation; 6, hospitalized and receiving mechanical ventilation; and 7, death.
Secondary outcomes included clinical status at 7 days, evaluated with the use of a six-level ordinal scale (see below and see the Supplementary Appendix); an indication for intubation within 15 days; the receipt of supplemental oxygen administered by a high-flow nasal cannula or noninvasive ventilation between randomization and 15 days; duration of hospital stay; in-hospital death; thromboembolic complications; acute kidney injury; and the number of days alive and free from respiratory support up to 15 days.
A day alive and free from respiratory support was defined as any day in which the patient did not receive supplemental oxygen or invasive or noninvasive mechanical ventilation, from randomization to day 15. Patients who died during the 15-day window were assigned a value of 0 days alive and free from respiratory support in this assessment.
Safety outcomes are listed in the Supplementary Appendix. All the trial outcomes were assessed by the site investigators, who were aware of the trial-group assignments (except as noted above for patients who had been discharged before day 15 and who were assessed for the primary outcome by means of a blinded telephone interview). No formal adjudication of trial outcomes was performed.
SAMPLE-SIZE CALCULATION AND PROTOCOL CHANGES
We had originally planned for the trial to include 630 patients, using the intention-to-treat analysis population, with a six-level ordinal outcome as the primary outcome, as described in the Supplementary Appendix.
However, before the first interim analysis was conducted, we changed the primary-outcome assessment to the seven-level ordinal scale and the main analysis population from the intention-to-treat population to a modified intention-to-treat population that included only patients with a diagnosis of Covid-19 that had been confirmed by reverse-transcriptase–polymerase-chain-reaction (RT-PCR) testing (using the test available at each site).
The change to the use of the seven-level ordinal scale was adopted because on April 10, 2020 (before the first enrolled patient had reached 15 days of follow-up), we established the capability to obtain 15-day information on limitations on activities with the use of blinded telephone interviews.
We therefore added another level to the six-level ordinal outcome, dividing the first level (not hospitalized) into two levels (level 1, not hospitalized and with no limitations on activities; and level 2, not hospitalized but with limitations on activities).
The change to the modified intention-to-treat population was adopted because, under the hypothesis that treatment would have beneficial effects on the primary outcome only for patients who had a confirmed diagnosis, the inclusion of unconfirmed cases would decrease the estimated effect size and power.
s a related change, we added external adjudication of unconfirmed cases, which were classified as probable, possible, or probably not Covid-19 (see the Supplementary Appendix).
The sample size was revised with the use of the overall distribution of the seven-level ordinal outcome at day 15 observed among the first 120 patients, with the levels 1 through 7 having the following proportions of patients: 60%, 19%, 7%, 1%, 1%, 5%, and 7%, respectively.
With 630 patients who had undergone randomization and 510 patients included in the modified intention-to-treat analysis, we calculated that the trial would have 80% power to detect an odds ratio of 0.5 between groups (two-by-two comparisons), at a significance level of 5% and with Bonferroni adjustment for multiple comparisons (α=5%, divided by 3 for each comparison).13
The primary outcome was analyzed by mixed ordinal logistic regression with random intercept according to site, assuming proportional odds. We report all two-by-two comparisons. Binary outcomes were assessed with the use of a mixed logistic-regression model, except for in-hospital mortality, which was assessed with a Cox proportional-hazards model.
Continuous outcomes were evaluated by means of generalized linear regression or mixed models for repeated variables, as appropriate. All models were adjusted for age and the use of supplemental oxygen at admission.
We also performed sensitivity analyses that included all the patients who had undergone randomization (intention-to-treat population) and sensitivity analyses for the primary outcome for the following groups: patients with definitive, probable, or possible Covid-19; and patients with definitive or probable Covid-19.
Two additional populations were considered. An efficacy population included patients with a confirmed diagnosis who received at least one dose of the assigned trial drug. The safety population included patients according to the medications received, regardless of the assigned trial group or the result of Covid-19 testing.
We planned three interim analyses, to be conducted when 120 patients, 315 patients, and 504 patients had completed 15 days of follow-up. However, only the first interim analysis was conducted. Owing to faster-than-expected enrollment, primary-outcome data for the second and third interim analyses were available only after trial recruitment was finished. After discussion with the data and safety monitoring committee, the second and third interim analyses were cancelled.
The data and safety monitoring committee used Haybittle–Peto14 stopping boundaries, with a P-value threshold of less than 0.001 to interrupt the trial for safety and a P-value threshold of less than 0.0001 to interrupt the trial for efficacy. We did not adjust the final values of the hypothesis test for sequential analyses.
Analyses were performed with the use of R software (R Core Team).15 P values for the primary outcome were adjusted with the use of Bonferroni correction. No P values are reported for secondary outcomes; the widths of the confidence intervals for the secondary outcomes have not been adjusted for multiple comparisons, so the intervals should not be used to infer definitive treatment effects.
P values for the safety analyses were not adjusted given the importance of identifying potential signals of harm. Additional details about the statistical analyses are provided in the Supplementary Appendix.
CHARACTERISTICS OF THE PATIENTS
We recruited 667 patients, including 504 patients with confirmed Covid-19. The numbers of enrolled patients according to site are presented in Table S1 in the Supplementary Appendix. A total of 217 patients were randomly assigned to receive hydroxychloroquine plus azithromycin, 221 to receive hydroxychloroquine, and 229 to receive standard care (control group) (Fig. S1).
The first patient underwent randomization on March 29, 2020; the last patient underwent randomization on May 17, 2020; and follow-up was completed on June 2, 2020. Two patients were excluded after randomization (1 withdrew consent after randomization and 1 had been enrolled twice). The 15-day follow-up was completed for all the remaining 665 patients.
The characteristics of the patients are shown in Table 1 and Table S2. Most patients (584 patients [87.8%]) underwent randomization within 10 days after symptom onset. The mean age of the patients was 50 years, and 58% of all the included patients were men. A total of 42% of the patients were receiving supplemental oxygen at baseline. The baseline data for the modified intention-to-treat population are shown in Table S3.
A comparison between the patients in the modified intention-to-treat population and those without a confirmed diagnosis of Covid-19 (161 patients) is shown in Table S4. Patients without a confirmed diagnosis of Covid-19 had a higher prevalence of chronic pulmonary obstructive disease or smoking, a lower prevalence of diabetes, and were less frequently receiving supplemental oxygen than patients who had a confirmed diagnosis. Details concerning adherence to the trial regimen and the use of other medications are presented in Tables S5 and S6, respectively.
The primary outcome (status on the seven-point ordinal scale at day 15) was assessed in all patients who were still in the hospital on day 15 exactly and in outpatients (by means of telephone interview) as close to day 15 as possible (see the Supplementary Appendixand Fig. S2).
Among patients with confirmed Covid-19, there were no significant between-group differences in the proportional odds of having a higher (worse) score on the seven-point ordinal scale at 15 days (hydroxychloroquine plus azithromycin vs. control: odds ratio, 0.99; 95% confidence interval [CI], 0.57 to 1.73; P=1.00; hydroxychloroquine alone vs. control: odds ratio, 1.21; 95% CI, 0.69 to 2.11; P=1.00; and hydroxychloroquine plus azithromycin vs. hydroxychloroquine alone: odds ratio, 0.82; 95% CI, 0.47 to 1.43; P=1.00) (Table 2). The distribution of patients’ scores on the seven-level ordinal scale at 15 days is shown in Figure 1.
The estimates and standard errors for the mixed-model analysis of the primary outcome are shown in Table S7. The distribution of patients in the ordinal-scale categories over time is shown in Figure 2. In this figure, levels 1 and 2 of the seven-level scale are combined (equivalent to the six-level scale previously described) because data on activity limitation were not available on a daily basis for outpatients.
In the intention-to-treat analysis, there was also no significant effect of treatment with either hydroxychloroquine plus azithromycin or hydroxychloroquine alone as compared with the control group (Table S8). Other sensitivity analyses showed similar results (Table S9). The results for the primary outcome were not different across the three prespecified subgroups (Table S10).
There were no significant differences in any of the secondary outcomes (Table 2). A total of 43 patients received mechanical ventilation during the first 15 days (11.0% of the patients assigned to receive hydroxychloroquine plus azithromycin, 7.5% of those in the hydroxychloroquine-alone group, and 6.9% of those in the control group). The mean (±SD) numbers of days alive and free from respiratory support were 11.1±4.9 in the group assigned to receive hydroxychloroquine plus azithromycin, 11.2±4.9 in the hydroxychloroquine-alone group, and 11.1±4.9 in the control group.
A total of 18 patients died in the hospital during the trial (5 patients assigned to receive hydroxychloroquine plus azithromycin, 7 in the hydroxychloroquine-alone group, and 6 in the control group). There were no significant between-group differences with regard to the secondary outcomes of thromboembolic complications or acute kidney injury within 15 days, either in the prespecified analyses (Table 2) or in post hoc analyses that accounted for the competing risk of death (Table S11). Marginal estimates of effects for the primary and secondary outcomes are shown in Table S12.
Adverse events in the safety population are reported in Table 3. More adverse events were reported in patients who received hydroxychloroquine plus azithromycin (39.3%) or hydroxychloroquine alone (33.7%) than in those who received azithromycin alone (18.0%) or none of the trial drugs (22.6%).
Serious adverse events occurred in nine patients (Table 3). Prolongation of the QTc interval was more common in patients receiving hydroxychloroquine plus azithromycin or hydroxychloroquine alone than in patients in the control group; however, fewer patients in the control group had serial electrocardiographic studies performed during follow-up than did patients in the other two groups.
Elevation in liver-enzyme levels was more common in patients receiving hydroxychloroquine plus azithromycin than in the control group. Adverse events in the intention-to-treat population and in the modified intention-to-treat population are shown in Tables S13 and S14, respectively.
In this open-label, multicenter, randomized, controlled trial involving hospitalized patients with confirmed mild-to-moderate Covid-19, a 7-day course of hydroxychloroquine either with azithromycin or alone did not result in better clinical outcomes as measured by a seven-level ordinal scale at 15 days. There was also no effect on any of the secondary outcomes. Occurrence of any adverse event, elevation of liver-enzyme levels, and prolongation of the QTc interval was more frequent in patients receiving hydroxychloroquine with azithromycin or hydroxychloroquine alone than in those receiving neither agent.
The prescription of short courses (<28 days) of hydroxychloroquine or chloroquine in the United States increased almost 2000% between March 21, 2019, and March 21, 2020, with a subsequent decrease.16 In Brazil, hydroxychloroquine has been formally recommended for the treatment of Covid-19 by the Ministry of Health since March 25, 2020, for severe cases and since May 20, 2020, for mild cases.5,6
However, no clinical benefit has been observed to date in randomized, controlled trials evaluating hydroxychloroquine for the treatment of Covid-19.9-11 In addition, higher doses of chloroquine (600 mg twice daily for 10 days) were possibly associated with higher mortality.17
Our trial enrolled patients with mild-to-moderate Covid-19 who were receiving no more than 4 liters per minute of supplemental oxygen. Hydroxychloroquine was administered relatively early after symptom onset (median, 7 days), which is earlier than the median time from symptom onset to treatment in a trial of remdesivir treatment for Covid-19.18Furthermore, the addition of azithromycin did not improve outcomes as had been suggested by observational case series.4
Our trial has several limitations. First, although the point estimate of effect suggests no major difference between the groups with respect to the primary outcome, the trial cannot definitively rule out either a substantial benefit of the trial drugs or a substantial harm. For the comparison between hydroxychloroquine and control, for example, our data are compatible with odds ratios as low as 0.69 and as high as 2.11.
Second, the trial was not blinded. Third, despite intense efforts to maintain adherence to the assigned treatments, a lack of medications that were perceived as beneficial by clinicians and patients led to some protocol deviations. Fourth, the use of hydroxychloroquine plus azithromycin was widespread among patients hospitalized with Covid-19 in participating hospitals.
The enrollment of patients with no previous use of these medications was challenging, so we decided to enroll patients provided that their previous use since the onset of symptoms was limited to 24 hours.
Finally, although the median time from symptom onset to randomization was 7 days, we included patients up to 14 days after the beginning of symptoms; it is conceivable that interventions that may limit viral replication (e.g., hydroxychloroquine) may be more effective earlier in the course of the disease.
In this trial involving hospitalized patients with mild-to-moderate Covid-19, we did not find a significant difference in a 15-day ordinal clinical-status outcome among groups that received standard care, hydroxychloroquine alone, or hydroxychloroquine plus azithromycin. Patients who received hydroxychloroquine, either with azithromycin or alone, had more frequent events of QTc interval prolongation and elevation of liver-enzyme levels than patients who did not receive either agent.
Supported by institutions participating in the Coalition Covid-19 Brazil and by EMS Pharma, which provided partial funding, the trial drugs, and logistic support.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
Drs. Cavalcanti and Zampieri contributed equally to this article.
This article was published on July 23, 2020, at NEJM.org.
A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.