Sulodexide in the treatment of patients with early stages of COVID-19: a randomised controlled trial

  1. Alejandro J. Gonzalez-Ochoa
  2. Joseph D. Raffetto
  3. Ana G. Hernández
  4. Nestor Zavala
  5. Obed Gutiérrez
  6. Arturo Vargas
  7. Jorge Loustaunau

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Background

Targeting endothelial cells has been suggested for the treatment of patients with COVID-19 and sulodexide has pleiotropic properties within the vascular endothelium that can prove beneficial to the same. We aimed to evaluate the effect of sulodexide when used in the early clinical stages of COVID-19.

Methods

We conducted a single-centre, outpatient setting, randomised controlled trial with a parallel-group design in Mexico. Including patients within three days of clinical symptom onset, who were at a high risk of severe clinical progression due to chronic comorbidities. Participants were randomly allocated to receive an oral dose of sulodexide (500 LRU twice a day) or the placebo for 21 days. Primary outcomes were need and length of hospitalisation, need and length of oxygen support.

Results

Between June 5 and August 30, 2020, 243 patients were included in the “per-protocol” analysis. One hundred twenty-four of them received sulodexide, while 119 received placeboes. At 21 days follow-up, 22 of 124 patients required hospitalisation in the sulodexide group compared to 35 of 119 in the placebo group [relative risk (RR), 0·6; 95% confidence interval (CI), 0·37-0·96; p=0·03]. Fewer patients required oxygen support in the sulodexide group [37 of 124 vs. 50 of 119; RR, 0·71; 95% CI, 0·5 to 1; p=0·05], and for fewer days (9±7·2 in the sulodexide group vs. 11·5±9·6 in the placebo group; p=0·02). There was no between-group difference concerning the length of hospital stay.

Interpretation

Early intervention in COVID-19 patients with sulodexide reduced hospital admissions and oxygen support requirements, although with no significant effect on mortality. This has beneficial implications in the patient well-being, making sulodexide a favourable medication until an effective vaccine or an antiviral becomes available.

Funding

Researcher independently initiated, partially funded by Alfasigma, Mexico.

Listed in the ISRCTN registry under ID ISRCTN59048638 .

Article activity feed

  3. ScreenIT

    SciScore for 10.1101/2020.12.04.20242073: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: We conducted this trial according to the Declaration of Helsinki, and it was board reviewed by the Universidad Autonoma de Baja California Faculty of Medicine Mexicali Ethics and Investigation Committee, being designated with approval number FMM/CEI/0011/2020-2.
    Consent: If eligible, an informed consent form was signed, and the patient was scheduled at the earliest for blood exams and the COVID-19 polymerase chain reaction (PCR) test.
    RandomizationStudy design: This is a prospective, randomised placebo-controlled trial with a parallel-group design evaluating the clinical outcome of consecutive patients who suffer early clinical stages of COVID-19.
    BlindingAs a result of local logistic limitations imposed due to the regional pandemic lockdown, as well as to verify timely medication dispensation, the lead researcher was not blinded to group allocation.
    Power Analysisnot detected.
    Sex as a biological variableInclusion criteria were as follows: male or female, age over 40 years, with suspected COVID-19 clinical symptom within 3 days of onset or less and high risk (>50%) of a severe clinical disease progression according to the percentage of risk given by the COVID-19 Health Complication (C19HC) calculator (IMSS, Gobierno de Mexico),21 which considers different chronic comorbidities described in table 1.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Estimates of risk ratios are presented with 95% Cis, and were calculated using the MedCalc software (MedCalc Software Ltd., Olsted,Belgium).
    MedCalc
    suggested: (MedCalc, RRID:SCR_015044)
    The SPSS software (IBM SPSS Statistics for Windows, version 26, IBM Corp., Armonk, NY, USA) was used for data analysis.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This trial does pose certain acknowledgeable limitations. Numerous asymptomatic carriers and lack of widespread diagnostic testing worldwide make it difficult to establish a real incidence of the disease, affecting accurate sample size calculations. With a significant part of the trial taking place in an outpatient setting, we did not foresee some of the logistic and infrastructure limitations due to the region’s pandemic lockdown. Key members of the staff were unavailable during part of the trail which forced the lead researcher to undertake data managing duties, breaking his blinding to group allocations. Other restrictions were also experienced in the hospital setting, for example, the impossibility to perform post-mortem examination. The different numbers and types of medications prescribed to the study population were very heterogenic. Moreover, there existed a noticeable difference between the prescription from primary physicians in the private sector vs. government care centres. Although evenly distributed among groups, the above factors should be taken into consideration during the interpretation of the study results. There is also reasoning for a later exploratory trial from an economic viewpoint. A significant benefit could be found when considering the total number of patient-hospital days (number of patients × mean number of hospital LOD) of 136 in the sulodexide group vs. 273 in the placebo group, with the consumed resources and cost 1-patient/day can represent. ...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    ISRCTN59048638NANA

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.12.04.20242073v1 on medRxiv