Large French Real-World Observational Study Reveals Hydroxychloroquine & Azithromycin Associated with Reduction in Hospitalization & Death for COVID-19 Patients

Jul 3, 2020 | COVID-19, France, Hydroxychloroquine, IHU Méditerranée Infection, News, Positive Results, SARS-CoV-2

Large French Real-World Observational Study Reveals Hydroxychloroquine & Azithromycin Associated with Reduction in Hospitalization & Death for COVID-19 Patients

Led by IHU-Méditerranée Infection in Marseille, a group of French research centers initiated early and massive screening for SARS-CoV-2 (COVID-19) in a hospitalized patient demographic. The study team analyzed the treatment of hydroxychloroquine and azithromycin (HCQ-AZ) for those patients screened positive for SARS-CoV-2. Out of 3,737 patients screened positive for COVID-19, 3,119 were treated with HCQ-AZ. The French team found that treatment with HCQ-AZ decreased the risk of the COVID-19 patient needing transfer to the ICU or death. Overall, the use of HCQ-AZ was associated with a decreased risk of hospitalization. The retrospective study revealed that an early diagnosis as well as early isolation and early treatment of COVID-19 patients, with at least 3 days of HCQ-AZ, leads to a significantly better clinical outcome and an expedited viral load reduction than other treatments.

The Backdrop

This retrospective study, recently reported in Travel Medicine and Infectious Disease, was led by doctors at IHU-Méditerranée Infection, Marseille as well as Aix Marseille University, and AP-HM, Marseille, France. As the pandemic emanated out of Wuhan the French team studied data originating from Chinese doctors on the ground during the pandemic. They utilized some of that knowledge to design a strategy that included early massive screening using PCR, LDCT of the chest for positive patients, and early treatment with hydroxychloroquine (HCQ) coupled with azithromycin (AZ) once they discovered the positive effects the two had in vitro and in vivo against SARS-CoV-2.  The workload at the medical facility in Marseille greatly increased however the team could produce real-world data enabling a heretofore not available opportunity to describe the disease and management at the institute despite well-known limitations involved with observational studies.

Some Sizeable Real-World Numbers

The numbers were significant at IHU-Méditerranée Infection, Marseille including a total of 31,003 patients tested for SARS-CoV-2 (including 1,277 health care workers);3,525 hospitalized patients, 705 patients hospitalized in infectious disease units; 6,000 samples tested including 643 samples from health care workers; 4,786 samples inoculated and 1,908 SARS-CoV-2 strains isolated; 466 genomes sequenced and analyzed; 2,218 low-dose CT scans performed; 7,800 electrocardiograms performed and a total of 1,939 hydroxychloroquine dosages.

The Regimen

The team retrospectively reported that out of 3,737 screened COVID-19 patients, 3,119 (83.5%) were treated with HCQ-AZ (200 mg of oral HCQ, three times daily for ten days and 500 mg of oral AZ on day 1 followed by 250 mg daily during the next four days, respectively) ongoing for at least three days and 618 (16.5%) patients treated with other medications (“others”). The French team studied outcomes including 1) death rate 2) transfer to the intensive care unit (ICU), ≥10 days of hospitalization and viral shedding.

The Results

The French team reported that overall the treatment regimen of HCQ-AZ led to a decreased risk of transfer to the intensive care unit (ICU) as well as death (Hazard ratio 0.18 0.11-0.27), a decreased risk of hospitalization ≥ 10 days (odds rations 95% CI 0.38 0.27-0.54 (and shorted duration of viral shedding (time to negative PCR: HR 1.29 1.17-1.42).  They did observe OTc prolongation (>60 ms ) in 25 patients (0.67%) which led to a halting of that treatment in 12 cases including 3 cases with QTc> 500 ms.  The team observed absolutely no cases of sudden death.

The team can make the claim based on the observations, or retrospective analysis that It would appear that if patients diagnosed with SARS-CoV-2 are diagnosed, isolated and treated early and administered at least 3 days of HCQ-AZ that this led to significantly improved clinical outcomes as well as expedited viral load reduction when compared to other treatments.

Lead Research/Investigator

Didier Raoult, IHU-Méditerranée Infection, Marseille, France (corresponding author)

Note, there are dozens of participating study authors; for a list, see the source.

Call to Action: The Henry Ford Health System study plus this study are not hard evidence that Hydroxychloroquine is safe and effective for COVID-19, but they certainly contribute to a growing body of favorable research knowledge.  More studies are ongoing and TrialSite News will be reporting on them. Sign up for the daily newsletter.


  1. Karen P

    As a layman following your news, I would appreciate translations of abbreviations or statistics regarding study efficacy into popular language. Did 18% more in this study avoid ICU, (.18. 0.11-0.27)? Was it a 95% lower likelihood of hospitalization longer than 10 days?
    Thank you for all you are doing!

    • TrialSite

      HCQ-AZ Follow-Up: Semi-Plain English Translation

      Our recent article about a French observational study, showing Hydroxychloroquine/Azithromycin reducing hospitalizations and deaths, left some questions as to the real-life meaning of some of the technical verbiage. The story described a “hazard ratio” for the study results. In simplest form, this phrase means the chance of an event happening in a treatment arm divided by the chance of the event happening in the control arm, or vice versa. Other methodology issues we hope to simplify include those relating to odds ratios and viral-shedding duration.

      “Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis,” is the article under discussion. It records that 3,119 persons were treated with the HCQ-AZ combination, and that study measures included death, ICU admission, ≥10 days of hospitalization, and viral shedding. The study, slightly simplified, notes that, 1) “Treatment with HCQ-AZ was associated with a decreased risk of transfer to ICU or death” with a hazard ratio of 0.18; 2) the treatment decreased hospitalization for ≥10 days with “odds ratios 95%;”and 3) there was a shorter duration of viral shedding with time to negative test “HR 1.29 1.17-1.42.” The mean hospital time for the HCQ-AZ group was 7.3 days, while the other groups showed 9.2.The patients hospitalized for ≥10 days Included 3.5% in the HCQ-AZ group and 14.2% in the other treatment groups.

      The NIH offers some general points to keep in mind: “The difference between hazard-based and time-based measures is analogous to the odds of winning a race and the margin of victory. The hazard ratio is the odds of a patient’s healing faster under treatment but does not convey any information about how much faster this event may occur.” After some technical details, NIH helpfully notes:

      “There is an alternative interpretation of the hazard ratio that may be intuitively easier to understand. The hazard ratio is equivalent to the odds that an individual in the group with the higher hazard reaches the endpoint first. Thus, in a clinical trial examining time to disease resolution, it represents the odds that a treated patient will resolve symptoms before a control patient. Stated another way, for any randomly selected pair of patients, one from the treatment group and one from the control group, the hazard ratio is the odds that the time to healing is less in the patient from the treatment group than in the patient from the control group.”

      In our context, the 0.18 result means that there were only 18 negative events in the treatment group for every 100 such events in other groups.

      Turning again to the NIH, an “odds ratio (OR) is a measure of association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure.” An OR of less than one means that an intervention is working better than the control. So here, the “95%” under decreased hospitalizations means there is a 95% certainty for a specific designation of the results. The viral shedding information also uses the phrase “hazard ratio.” In this context, “A hazard ratio (HR) of <1 indicated prolonged viral RNA shedding.”

      TrialSite News will continue to decipher Pharma science for our readers, and in the world of science there is always more to learn.

  2. TomG

    I wouldn’t trust anything coming from the Raoult camp after his shoddy initial studies.

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