Covid-19 living Data

Colchicine vs Standard care/Placebo (RCT)

Hospitalized patients

FOREST PLOTS -2022-06-10

Studies description

Trial NCT04367168
Publication COLCHIVID - Absalon-Aguilar A, J Gen Intern Med (2021) (published paper)
Dates: 2020-05-01 to 2021-04-30
Funding: Public/non profit (Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán.)
Conflict of interest: No

Methods
	RCT Blinding: triple blinding
	Location : Multicenter / Mexico Follow-up duration (days): 100
Inclusion criteria	Hospitalized Adult patients aged 18 to 70 years Tested positive for at least one of the following COVID-19 diagnostic assays - polymerase chain reaction (PCR) for SARS-CoV-2 in nasopharyngeal swab, rapid antigen test, or serum anti-SARS-CoV-2 IgG antibodies Severe COVID-19 according to the following definition - respiratory failure, respiratory rate ≥ 30 bpm, oxygen saturation (SpO2) ≤ 93% at rest, PaO2/FiO2 ≤ 300 mmHg
Exclusion criteria	Over 70 years old Chronic liver or kidney failure Pregnant Have puerperium Receiving any drug with known interaction with colchicine Patients treated with antimalarial drugs, azithromycin, convalescent plasma, remdesivir, tocilizumab, or baricitinib
Interventions
	Treatment Colchicine Initial dose: 1.5 mg orally once-off - Maintenance dose: 0.5 mg orally twice a day for 10 days.
	Control Placebo
Participants
	Randomized participants : Colchicine=56 Placebo=60
	Characteristics of participants N= 116 Mean age : NR 76 males Severity : Mild: n=0 / Moderate: n=0 / Severe: n=116 Critical: n=0
Primary outcome
	In the register Number of patients with improvement in body temperature, myalgia, arthralgia, total lymphocyte count, D-dimer, fibrinogen and ferritin levels [ Time Frame: Up to 24 days ] Progression to severe disease [ Time Frame: Up to 10 days ]
	In the report Death or progression to critical disease, defined as multiple organ failure, shock, or need for invasive mechanical ventilation.
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Not reported
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article, the study registry and contact with authors was used in data extraction and risk of bias assessment. The protocol and statistical analysis plan were not available. The registry primary outcome does not reflect the reported primary outcome. Some outcomes in the paper (e.g. adverse events, mortality) were not in the registry but were defined in the protocol. There is no change from the trial registration in the intervention and control treatments, however the inclusion criteria has both mild and severe patients in the registry, while the paper only included severe patients. The study (n=116) did not achieve the target sample size specified in the trial registry (n=174) as the trial was terminated early because the treatment showed not effect on the primary outcome after the second interim analysis. The study was updated on April 13th, 2022 with data gained from contact with authors.

Trial *
Publication Alsultan M, Interdiscip Perspect Infect Dis (2021) (published paper)
Dates: 2021-08-01 to 2021-08-30
Funding: Not reported/unclear
Conflict of interest: No

Trial NCT04724629
Publication STRUCK - Bonifacio L, SSRN (2022) (preprint)
Dates: 2021-01-06 to 2021-07-09
Funding: Mixed (Rede Vírus (MCTI - Ministerio Da Ciencia, Tecnologia e Inovacoes) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) (National Council for Scientific and Technological Development). Company Clinigen provided bottles of Interleukin-2 (ProleukinTM) free of charge.)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / Brazil Follow-up duration (days): 45
Inclusion criteria	18 Years and older hospitalized moderate to severe presentation of Covid-19 positive result in the quantitative real-time PCR (qPCR) test for SARS-CoV-2 in the respiratory tract pneumonia confirmed by chest imaging and 1) Respiratory rate ≥ 24 IRPM (for adults) or 2) O2 saturation <93% or 3) No improvement in O2 saturation, despite oxygen supply or Arterial hypotension or 4) Changes in capillary filling time or 5) Changes in the level of consciousness or 6) Oliguria.
Exclusion criteria	Age <18 years Refuse to sign the Informed Consent Form Patient's decision that their involvement is not in their interest Severe known liver disease (eg cirrhosis, with aminotransferase levels> 5 times the reference value limit) Pregnancy or breastfeeding period Severe bacterial infection Severe diarrhea Diverticulitis or intestinal perforation Infection known as HIV Presence of one of the following uncontrolled or unstable cardiovascular diseases: stroke, ECG confirmed acute ischemia or myocardial infarction and / or clinically significant dysrhythmia Known history of gastrointestinal bleeding, uncontrolled peptic ulcer or uncontrolled duodenal ulcer Known history of hemophilia or other bleeding disorders History of organ transplantation, congenital immunodeficiency.
Interventions
	Treatment Ixekizumab 80 mg/ week subcutaneously, once a week for 4 weeks or until discharge. Interleukin-2 1.5 million IU/day subcutaneously for 7 days or until discharge. Colchicine Initial dose: 0.5 mg orally every 8 hours for 3 days - Maintenance dose: 0.5 mg orally twice daily for 4 weeks (+/-7 days)
	Control Standard care
Participants
	Randomized participants : Ixekizumab=16 Interleukin-2=14 Colchicine=14 Standard care=16
	Characteristics of participants N= 60 Mean age : NR 37 males Severity : Mild: n=0 / Moderate: n=37 / Severe: n=17 Critical: n=6
Primary outcome
	In the register Ordinal scale of seven World Health Organization (WHO) categories of IL-17 inhibitor versus low dose IL-2 versus indirect IL-6 inhibitor (colchicine) versus standard treatment in the treatment of severe COVID-19 [ Time Frame: On the 21st day of study, since inclusion. ] proportion of patients with clinical improvement, defined by an increase of two points in the ordinal scale of seven WHO categories
	In the report Proportion of patients with clinical improvement, defined by an increase of two points on the WHO’s ordinal scale at day 28.
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Not reported
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the preprint and the published conference abstract, the study registry was used in data extraction and risk of bias assessment. Neither the protocol nor statistical analysis plan were available. There is no change from the trial registration in the intervention and control treatments. The timeframe for the registry primary outcome (21 days) does not reflect the reported timeframe for the primary outcome (28 days). Many outcomes from the registry are not reported in the abstract (e.g. need for mechanical ventilation). The preprint reports on an interim analysis and the study achieved the target sample size (n=60) specified in the trial registry. This study was updated on June 9th 2022 with data from the preprint.

Trial NCT04326790
Publication Deftereos S, JAMA (2020) (published paper)
Dates: 03apr2020 to 27apr2020
Funding: Private (The study was funded by ELPEN Pharmaceuticals, Acarpia Pharmaceuticals, and Karian Pharmaceuticals.)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / Greece Follow-up duration (days): 21
Inclusion criteria	"1. Subjects >18 years old with laboratory confirmed SARS-COV-2 [by reverse transcription polymerase chain reaction (RT PCR)], who present with clinical symptoms including body temperature >37.5°C. AND 2. At least two of the following criteria: 6) persistent cough 7) persistent throat pain 8) anosmia, ageusia 9) asthenia 10) Arterial blood partial pressure of oxygen (PaO2)<95 mmHg."
Exclusion criteria	"1. Pregnancy, breastfeeding or unwillingness to take effective contraceptive measures during the clinical trial in women and men of childbearing potential. 2. Known hypersensitivity to colchicine or to any of the excipients of the product (lactose, gum arabic, sucrose, magnesium stearate, microcrystalline cellulose, polyvinylpyrrolidone, methylene casein, erythrosine lacquer). 3. Severe hepatic impairment. 4. Estimated glomerular filtration rate (eGFR) <20 ml/min/1.73m2. 5. Treating physician's clinical judgement that the patient will require mechanical respiratory support within 24 hours. 6. Any condition or circumstances which, at the discretion of the treating physician, would prevent the indicated follow-up of the participant. 7. Electrocardiographic QTc interval>450 msec. 8. Participation in a clinical trial with an investigational product (drug or medical device) or intervention. 9. Under treatment with colchicine for other indications. 10. A subject that, at the discretion of the Investigator, is unable to comply with the requirements of the clinical trial or his/her participation in it may put him/her at unacceptable risks for his/her health. 11. A subject undergoing haemodialysis. 12. Severe gastrointestinal failure, severe gastrointestinal disorders, or stomach ulcer. 13. Haematological disorders, such as blood diseases. 14. Under treatment or had received within the past 14 days drugs belonging to the classes of P-glycoprotein inhibitors or CYP3A4 enzyme inhibitors."
Interventions
	Treatment Colchicine Initial dose: 1.5 mg orally followed by 0.5 mg an hour later if no adverse effect - Maintenance dose: 0.5 mg twice a day for a maximum of 21 days
	Control Standard care
Participants
	Randomized participants : Colchicine=56 Standard care=54
	Characteristics of participants N= 110 Mean age : NR 61 males Severity : Mild: n=0 / Moderate: n=102 / Severe: n=3 Critical: n=0
Primary outcome
	In the register Clinical deterioration in the semiquantitative ordinal scale suggested by the WHO R&D committee [ Time Frame: 3 weeks ] Time to clinical deterioration (2 levels in the WHO R&D Blueprint scale) Maximal concentration of cardiac troponin [ Time Fr
	In the report The coprimary end points of the biochemical phase were the difference in maximal high-sensitivity cardiac troponin (hs cTn) levels between the 2 groups and the time for C-reactive protein to reach levels greater than 3 times the upper reference limit
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to all available versions of the published article, the study registry, protocol, and statistical analysis plan were used in data extraction and risk of bias assessment. There is no change from the trial registration in the intervention and control treatments. Two types of primary outcomes were presented - a biochemical and a clinical. The biochemical primary outcome in the report partially reflects the primary outcome indicated in the registry. Stated in the registry, it was "Maximal concentration of cardiac troponin [ Time Frame: 10 days ], Maximal concentration of high-sensitivity cardiac troponin" while in the report it was "the difference in maximal high-sensitivity cardiac troponin (hs cTn) levels between the 2 groups and the time for C-reactive protein to reach levels greater than 3 times the upper reference limit." The study did not reach its recruitment target of 180 patients as specified in the registry and protocol "because of slow enrollment as a result of the rapid flattening of the curve of COVID-19 cases in Greece."

Trial NCT04328480
Publication ECLA PHRI COLCOVID - Diaz R, JAMA Netw Open (2021) (published paper)
Dates: 2020-04-17 to 2021-03-28
Funding: Mixed (The Population Health Research Institute contributed fees to the investigators. Fundacion ECLA funded all other aspects of the trial. Colchicine was donated by Spedrog Caillon to some centers lacking it.)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / Argentina Follow-up duration (days): 28
Inclusion criteria	Hospitalized adults (age 18 years) confirmed or suspected SARS-CoV-2 infection admitted to the hospital with symptoms suggestive of COVID-19 (eg, fever or equivalent, loss of smell and/or taste, fatigue) severe acute respiratory syndrome characterized by shortness of breath (dyspnea) or typical or atypical pneumonia on imaging, or oxygen desaturation (as measured by pulse oximetry [SpO2] <= 93%).
Exclusion criteria	Clear indications or contraindications for the use of colchicine pregnancy or breastfeeding chronic kidney disease (creatinine clearance <15 mL/min/m2 [to convert to mL/s/m2, multiply by 0.0167]) negative result on a reverse transcription–polymerase chain reaction (RT-PCR) test for SARS-COV-2 available before randomization.
Interventions
	Treatment Colchicine Initial dose: 1.5 mg orally followed by 0.5 mg orally within 2 hours - Maintenance dose: 0.5 mg orally twice a day for 14 days or until discharge.
	Control Standard care
Participants
	Randomized participants : Standard care=639 Colchicine=640
	Characteristics of participants N= 1279 Mean age : NR 830 males Severity : Mild: n=196 / Moderate: n=995 / Severe: n=23 Critical: n=65
Primary outcome
	In the register All-cause mortality [ Time Frame: During hospitalization or until death, whichever comes first, assessed up to 30 days ]
	In the report 1) Composite of a new requirement for mechanical ventilation or death evaluated at 28 days after randomization; 2) Death assessed at 28 days after randomization.
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article, the trial registry, protocol, statistical analysis plan and supplementary appendices were used in data extraction and assessment of risk of bias. The primary outcome in the article reflected that in the registry, but differed from that in the original protocol. Due to low recruitment and low likelihood of reaching the original estimated sample size of 2500 patients, with the aim of reducing the trial sample size and prior to knowing the results, the executive committee decided to change the single primary outcome to two co-primary outcomes: the original primary outcome (all-cause mortality); a composite secondary outcome (new need for mechanical ventilation or death). The trial (n = 1279) achieved its amended target sample size (n = 1200).

Trial NCT04381936 ; ISRCTN50189673
Publication RECOVERY (COL) - Horby P, Lancet Respir Med (2021) (published paper)
Dates: 2020-11-27 to 2021-03-04
Funding: Mixed (UK Research and Innovation (Medical Research Council); National Institute of Health Research; Wellcome Trust;. Bill and Melinda Gates Foundation; Foreign, Commonwealth and Development Office; Health Data Research UK; Combiphar (drug donation))
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / UK, Indonesia, Nepal Follow-up duration (days): 28
Inclusion criteria	Admitted to hospital clinically suspected or laboratory confirmed SARS-CoV-2 infection no medical history that might, in the opinion of the attending clinician, put the patient at significant risk if they were to participate in the trial.
Exclusion criteria	Children and pregnant women patients with severe liver impairment, significant cytopaenia, concomitant use of strong CYP3A4 or P-glycoprotein inhibitors, or hypersensitivity to lactose.
Interventions
	Treatment Colchicine Initial dose: 1 mg after randomization and 500 mcg 12 hours later - Maintenance dose: 500 mcg twice daily orally or by nasogastric tube for 10 days or until discharge.
	Control Standard care
Participants
	Randomized participants : Standard care=5730 Colchicine=5610
	Characteristics of participants N= 11340 Mean age : NR 7909 males Severity : Mild: n=* / Moderate: n=* / Severe: n=3034 Critical: n=529
Primary outcome
	In the register All-cause mortality [ Time Frame: Within 28 days after randomisation ]
	In the report 28-day mortality
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication:
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the pre-print article, the trial registries, protocol and statistical analysis plan were used in data extraction and assessment of risk of bias. There were no substantive differences between the pre-print article and the registry, protocol or statistical analysis plan on procedures, interventions or outcomes. Whereas in the trial registry (clinicaltrials.gov) colchicine was only allowed in women ≥55 years old, in the report only pregnant women were disallowed from the treatment. Recruitment was stopped on the advice of the independent data monitoring committee following a routine interim analysis that revealed there was no convincing evidence that further recruitment to the colchicine comparison would provide conclusive proof of worthwhile mortality benefit either overall or in any pre-specified subgroup. On October 20th, he extraction and risk of bias were updated with the information from the published article.

Trial RBR-8jyhxh
Publication Lopes MIF, RMD Open (2021) (preprint)
Dates: 2020-04-11 to 2020-08-30
Funding: Public/non profit (FAPESP, CNPq and CAPES grants.)
Conflict of interest: No

Methods
	RCT Blinding: Double blinded, no restrictions
	Location : Single center / Brazil Follow-up duration (days): 15
Inclusion criteria	Individuals hospitalized with moderate or severe forms of COVID-19 diagnosed by RT-PCR in nasopharyngeal swab specimens and lung computed tomography scan involvement compatible with COVID-19 pneumonia older than 18 years body weight > 50 kg normal levels of serum Ca2+ and K+ QT interval < 450 ms at 12 derivations electrocardiogram (according to the Bazett formula) and negative serum or urinary β-HCG if woman under 50.
Exclusion criteria	Mild form of COVID-19 or in need for ICU admission diarrhea resulting in dehydration known allergy to colchicine diagnosis of porphyria, myasthenia gravis or uncontrolled arrhythmia at enrollment pregnancy or lactation metastatic cancer or immunosuppressive chemotherapy regular use of digoxin, amiodarone, verapamil or protease inhibitors chronic liver disease with hepatic failure inability to understand the Consent Form.
Interventions
	Treatment Colchicine 0.5 mg orally, twice daily for 5 days, then 0.5 mg twice daily for 5 days; if body weight ≥80 kg, the first dose was 1.0 mg
	Control Placebo
Participants
	Randomized participants : Placebo=37 Colchicine=38
	Characteristics of participants N= 75 Mean age : NR 33 males Severity : Mild: n=0 / Moderate: n=* / Severe: n=* Critical: n=*
Primary outcome
	In the register To evaluate the duration of oxygen therapy for both groups, measured in number of days of need of supplemental oxygen by catheter or masks. To evaluate the hospitalization time for both groups, measured in number of days from the admission to th
	In the report Time of need for supplemental oxygen; time of hospitalization; need for admission and length of stay in ICU; and death rate and causes of mortality
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to all available versions of the published/pre-print article, the study registry were used in data extraction and risk of bias assessment. No pre-specified statistical analysis plan nor protocol was available at the time but authors state that they will be made available as supplementary files in the journal. There is no change from the trial registration in the primary and secondary outcomes. The trial registry reported the intervention treatments as both chloroquine or hydroxychloroquine plus colchicine and the control treatments as both choloroquine or hydroxychloroquine plus placebo. The pre-print reported the intervention arm as colchicine and the control as placebo with choloroquine or hydroxychloroquine, among other drugs (azithromycin, unfractioned heparin and (if needed) methylprednisolone) as standard of care for the institution. The study was updated on March 19th, 2021 with data from the RMD Open publication. Results based on previous author contact were not considered, since recruitment was not done. Therefore, all results presented are based on the final and published report.

Trial NCT04350320 ; EUDRACT 2020-001511-2
Publication COL-COVID - Pascual-Figal DA, Int J Gen Med (2021) (published paper)
Dates: 2020-04-30 to 2020-12-04
Funding: Public/non profit (1) “Cardiology Research group” at the IMIB-Arrixaca and the University of Murcia, Murcia, Spain; 2) Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and Pro-CNIC Foundation.)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : * / Spain Follow-up duration (days): 28
Inclusion criteria	1) above 18 years old 2) SARS-CoV-2 infection confirmed by reverse-transcriptase polymerase chain reaction on nasal swab (RT-PCR) 3) admitted in hospital in the previous 48 hours with COVID-19 diagnosis 4)7-points WHO clinical status of 3, 4 or 5 (3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen by mask or nasal prongs 5. Hospitalized, non-invasive ventilation or high flow oxygen)
Exclusion criteria	1) invasive or noninvasive mechanical ventilation needed 2) established limitation of therapeutic effort 3)inflammatory bowel disease, chronic diarrhea or malabsorption 4)previous neuromuscular disease 5)any disease with an estimated vital prognosis under 1 year 6) severe renal insufficiency (glomerular filtration rate <30 mL/min/1.73m2) 7) medical history of cirrhosis, active chronic hepatitis or severe hepatic disease defined by liver transaminases levels threefold above the normal upper limit 8)previous colchicine treatment for other diseases 9) history of allergic reaction or significant sensitivity to colchicine 10) immunosuppressive agents, including corticoids, within the previous 6 months.
Interventions
	Treatment Colchicine Initial dose: 1.5 mg (1 mg and 0.5 mg two hours after) - first maintenance dose: 0.5 mg twice a day for 7 days - second maintenance dose: 0.5 mg once a day for 21 days. (Dose reduced by half in patients receiving ritonavir or lopinavir or with at least one of the following: reduced renal clearance (<50 mL/min/1.37m2), weight <70 kg or age >75 years old.)
	Control Standard care
Participants
	Randomized participants : Standard care=51 Colchicine=52
	Characteristics of participants N= 103 Mean age : NR 54 males Severity : Mild: n=34 / Moderate: n=69 / Severe: n=0 Critical: n=0
Primary outcome
	In the register 1) Changes in the patients' clinical status through the 7 points ordinal scale WHO R&D Blueprint expert group [ Time Frame: 7,14,28 Days ]; 2) Changes in IL-6 concentrations [ Time Frame: up to day 28. ]
	In the report 1) Change in the WHO 7-points ordinal clinical scale during the 28 days of treatment; 2) effect on IL-6 levels, as main surrogated marker of inflammatory response
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article, the trial registries and supplementary materials were used in data extraction and assessment of risk of bias. Neither protocol not statistical analysis plan was available. The primary outcomes in the article reflected those in the registry. Some secondary outcomes in the registry were not reported in the article. There was no change from the trial registration in the intervention and control treatments. The study (n = 103) achieved its target sample size (n = 102).

Trial IRCT20190810044500N5
Publication Pourdowlat G, Phytother Res (2022) (published paper)
Dates: 2020-03-26 to 2020-09-30
Funding: Not reported/unclear
Conflict of interest: No

Methods
	RCT Blinding: single blinding
	Location : Multicenter / Iran Follow-up duration (days): 14
Inclusion criteria	Aged 18–80 years confirmed to be COVID-19 positive according to PCR results or manifestations in CT scan evidence of moderate to severe lung involvement based on CT scan Female patients were informed they should not become pregnant until 30 days after the end of the study not taking colchicine during the last week (due to the half-life of 20–40 hr of the drug)
Exclusion criteria	Shock or hemodynamic instability a history of Crohn's or ulcerative colitis, diarrhea, or chronic malabsorption neuromuscular diseases eGFR <30 ml/min a history of cirrhosis, hepatitis, or severe liver disease had used colchicine for other conditions such as gout or Mediterranean fever a history of an allergic reaction to colchicine were receiving chemotherapy for cancer were pregnant or lactating
Interventions
	Treatment Colchicine Initial dose: 0.5 mg/day orally for up to 3 days -Maintenance dose: 1 mg/day orally for 12 days
	Control Standard care
Participants
	Randomized participants : Colchicine=102 Standard care=100
	Characteristics of participants N= 202 Mean age : NR 93 males Severity : Mild: n=0 / Moderate: n=* / Severe: n=* Critical: n=0
Primary outcome
	In the register Clinical symptoms including fever, cough, shortness of breath. Timepoint: The first, third, seventh, fourteenth and 6-8 days after entering the study. Method of measurement: questionnaire. Laboratory symptoms (ESR, CRP, NLR, LDH, ferritin, D-dimer, CBC diff). Timepoint: Hospitalization time and discharge time. Method of measurement: Blood test. O2sat at the time of hospitalization and discharge. Timepoint: The first, third, seventh, fourteenth and 6-8 days after entering the study. Method of measurement: Pulse Oximeter. Pulmonary infiltration findings on CT scan. Timepoint: Two weeks later and 6-8 weeks later. Method of measurement: CT-scan.
	In the report Clinical status distribution on chest CT evaluations
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: N
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article, the retrospective study registry was used in data extraction and risk of bias assessment. The protocol and statistical analysis plan were not available. As the registry was retrospective we were unable to determine if the intervention, sample size and analysis plan were determined a-priori. The primary outcome for the paper was unclear, while the registry had four primary outcomes. Some outcomes from the registry are not reported in the paper (e.g., Mortality and Need hospitalization in ICU).

Trial IRCT20200418047126N1
Publication Salehzadeh F, Research Square (2020) (preprint)
Dates: 2020-05-21 to 2020-06-20
Funding: Public/non profit (Ardabil University of Medical Sciences)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Single center / Syria Follow-up duration (days): *
Inclusion criteria	Oxygen saturation ≤93% plus at least one of the following: (1) respiratory rate ≥30 breaths/min, (2) infiltrates >50% on CT scan, and (3) arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen ratio (FiO2) <300 mmHg Adults (aged ≥18 years) positive PCR test of COVID-19 virus in specimens taken from the respiratory tracts patients with negative PCR test but had clinical signs and symptoms of viral illness accompanied with chest CT scan showing the radiologic findings of viral pneumonia, which was defined as new, unexplained, and bilateral infiltrates on the lungs
Exclusion criteria	Admitted for other conditions with oxygen saturation ≥94% without viral symptoms but had infiltrations on chest CT scan (mild form of COVID-19) received other antiviral or investigational therapies for COVID-19 expired or transmitted to ICU during the first 24 hours patients who committed with persistent treatment of steroid inhalers
Interventions
	Treatment Colchicine Initial dose : 1.5 mg orally followed by 0.5 mg 1 hour later on day 1, Maintenance dose: 0.5 mg orally twice daily for 4 days Budesonide 200 mcg inhaled twice daily for 5 days
	Control Standard care
Participants
	Randomized participants : Colchicine=14 Budesonide =14 Standard care=21
	Characteristics of participants N= 49 Mean age : NR 19 males Severity : Mild: n=0 / Moderate: n=* / Severe: n=* Critical: n=0
Primary outcome
	In the register NR
	In the report NR
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	*
General comment	Only the published article was available for data extraction and assessment of risk of bias. No registry, protocol or statistical analysis plan was available. No outcome was identified as primary in the article. It is not clear whether the study achieved a target sample size. No outcomes with clear time points relevant for COVID-NMA were reported.

Methods
	RCT Blinding:
	Location : Single center / Iran Follow-up duration (days): 22
Inclusion criteria	Pulmonary involvement seen in CT-Scan compatible with COVID-19 and Positive PCR of COVID-19
Exclusion criteria	Sensitivity to any medications of regimens, renal failure, heart failure, pregnancy, participating in another clinical study and refusal to participate in the study before or during the follow-up period
Interventions
	Treatment Colchicine 1 mg orally once a day for 6 days.
	Control Placebo
Participants
	Randomized participants : Colchicine=50 Placebo=50
	Characteristics of participants N= 100 Mean age : NR 41 males Severity : Mild: n=0 / Moderate: n=* / Severe: n=* Critical: n=*
Primary outcome
	In the register Hospitalization outcome, fever cessation, hospitalization time
	In the report (1) Length of hospitalization; (2) symptoms and (3) Co-existed disease.
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Not reported
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the preprint article, the trial registration was used for data extraction and risk of bias assessment. There were considerable differences between outcomes reported in the pre-print article and those in the study registry. Symptoms and co-existed disease were outcomes in the report but they were not specified in the registry. There was a difference in treatment duration between study registry and pre-print article.