Study Samaha A, Viruses 2021 has been retracted on October 26, 2021. The study was excluded from the analysis and grade assessment by December 17 the latest.
Study Pott-Junior H, 2021 (Toxicology Reports) retracted on May 11, 2022. FOREST PLOTS -2022-06-02
Trial NCT04716569
Publication Aref ZF, Int J Nanomed (2021) (published paper)
Dates: 2021-02-20 to 2021-03-30
Funding: Public/non profit (South Valley University, Faculty of Medicine)
Conflict of interest: No
Methods | |
RCT Blinding: Unblinded | |
Location :
Single center / Egypt Follow-up duration (days): * | |
Inclusion criteria |
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Exclusion criteria |
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Interventions | |
Treatment
Ivermectin 70 mcg/mL by intranasal spray twice a day |
|
Control
Standard care | |
Participants | |
Randomized participants : Ivermectin=57 Standard care=57 | |
Characteristics of participants N= 114 Mean age : NR 82 males Severity : Mild: n= 114/ Asymptomatic: n=0 | |
Primary outcome | |
In the register Progression of covid 19 clinical picture [ Time Frame: within 14 days after enrollement ] | |
In the report Clinical improvements of the presenting manifestations with recording the recovery duration for every manifestation | |
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 prospective trial registry was used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. There is no change from the trial registration in the intervention and control treatments. The extracted outcome (negative viral conversion was not explicitly included as an outcome in the registry (progress of Symptoms ( Fever ,Cough, Sore Throat, Myalgia, Diarrhea, Shortness of Breath) with radiological assessment and blood tests). The trial (n = 114) did not achieve its pre-stated target sample size (n = 150). |
Trial NCT04429711
Publication Biber A, medRxiv (2021) (preprint)
Dates: 2020-05-15 to 2021-01-30
Funding: No specific funding (None)
Conflict of interest: No
Methods | |
RCT Blinding: double blinding | |
Location :
Multicenter / Israel Follow-up duration (days): 14 | |
Inclusion criteria |
|
Exclusion criteria |
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Interventions | |
Treatment
Ivermectin Weight 40-69 kg = 12mg orally once a day for 3 days; weight ≥70kg =15mg orally once a day for 3 days |
|
Control
Placebo | |
Participants | |
Randomized participants : Ivermectin=57 Placebo=59 | |
Characteristics of participants N= 116 Mean age : NR 69 males Severity : Mild: n= 72/ Asymptomatic: n=17 | |
Primary outcome | |
In the register Viral clearance at day 6 [Time Frame: Outcome will be determined till 6 days post intervention] | |
In the report Viral clearance following a diagnostic swab taken on the sixth day (third day after termination of treatment) | |
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 pre-print article, the trial registry (dated June 12 2020) was used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. Due to delays in test results in the community, the inclusion criteria relating to time from testing to inclusion were slightly different in the report than in the registry in terms of time from symptom onset to testing. Some changes were made to the testing timepoints during the trial due to changes in national policies on discharge from isolation. The study achieved its target sample size. The registry was retrospective. The registry primary outcome reflects that reported in the preprint, however, the secondary outcomes reported in the registry (symptom clearance time, viral shedding duration) were not reported. |
Trial NCT04438850
Publication COVER - Buonfrate D, Int J Antimicrob Agents (2022) (published paper)
Dates: 2020-07-31 to 2021-06-10
Funding: Public/non profit (Italian Ministry of Health; Tablets of 9 mg ivermectin and of placebo were donated by Insud Pharma, Madrid.)
Conflict of interest: No
Methods | |
RCT Blinding: double blinding | |
Location :
Multicenter / Italy Follow-up duration (days): 30 | |
Inclusion criteria |
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Exclusion criteria |
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Interventions | |
Treatment
Ivermectin 600 600 mcg/kg once daily orally for 5 days Ivermectin 1200 1200 mcg/kg once daily orally for 5 days Ivermectin 600 mcg/kg once daily orally for 5 days |
|
Control
Placebo | |
Participants | |
Randomized participants : Ivermectin 600=29 Ivermectin 1200=32 Placebo=32 Ivermectin =61 | |
Characteristics of participants N= 154 Mean age : NR 69 males Severity : Mild: n= */ Asymptomatic: n=* | |
Primary outcome | |
In the register 1) SADR [ Time Frame: 14 days ] Number of serious adverse drug reaction; 2) Viral load [ Time Frame: Assessed at day 7 ] Quantitative viral load as measured by quantitative, digital droplet PCR | |
In the report 1) Nmber of SADRs; 2) Change in viral load at Day 7 with respect to baseline. at Day 7 | |
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 pre-print article, the study registry was used in data extraction and risk of bias assessment. The primary outcome indicated in registry reflects the primary outcome reported in the paper. The protocol was not available though mentioned in the article to be included in the supplementary appendix. The recruitment was stopped on 10th June, because of a dramatic drop of cases. Incidence of viral negative conversion outcome was reported for a timeframe within 14 days, hence likely cumulative. This study was updated on April 11th 2022, with data from the peer-reviewed publication. |
Trial NCT04390022
Publication SAINT - Chaccour C, EClinicalMedicine (2021) (published paper)
Dates: 2020-07-31 to 2020-09-11
Funding: Mixed (ISGlobal; University of Navarra. Unitaid; Spanish Ministry of Science and Innovation; Generalitat de Catalunya; Idipharma SL (placebo donation))
Conflict of interest: No
Methods | |
RCT Blinding: | |
Location :
Single center / Spain Follow-up duration (days): 28 | |
Inclusion criteria |
|
Exclusion criteria |
|
Interventions | |
Treatment
Ivermectin 400 mcg/kg orally once off. |
|
Control
Placebo | |
Participants | |
Randomized participants : Ivermectin=12 Placebo=12 | |
Characteristics of participants N= 24 Mean age : NR 12 males Severity : Mild: n= 24/ Asymptomatic: n=0 | |
Primary outcome | |
In the register Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment | |
In the report Proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment | |
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 supplementary appendices, the study registry, protocol and data analysis plan were used in data extraction and risk of bias assessment. There were no substantive differences between the pre-print article and the trial registry, study protocol and statistical analysis plan in population, procedures, interventions or outcomes. The study achieved its stated sample size.
Quote: "The placebo tablets did not match ivermectin in appearance, therefore, in order for the clinical team to remain blinded, treatment was administered under direct supervision by a nurse not participating in patient´s care. There was slow recruitment due to a sharp reduction in local transmission for 10 weeks after the lockdown of March-April 2020, the protocol was amended on September 2nd to extend the inclusion criteria from 48 to a maximum of 72 hours of cough or fever." This study was updated on January 28th, 2021 after publication of the study report. |
Trial NCT04784481
Publication Chahla R, Research Square (2021) (preprint)
Funding: Public/non profit (Ministry of Public Health, Tucumán, Argentina)
Conflict of interest: No
Methods | |
RCT Blinding: Unblinded | |
Location :
Multicenter / Argentina Follow-up duration (days): 28 | |
Inclusion criteria |
|
Exclusion criteria |
|
Interventions | |
Treatment
Ivermectin 24 mg orally every 7 days for 4 weeks |
|
Control
Standard care | |
Participants | |
Randomized participants : Standard care=144 Ivermectin=110 | |
Characteristics of participants N= 254 Mean age : NR 121 males Severity : Mild: n= 254/ Asymptomatic: n=0 | |
Primary outcome | |
In the register Proportion of patients with symptoms (fever, diarrhea, taste and/or smell disturbance, SpO2, polyarthralgia, headache, body pain, abdominal pain, ALRI symptoms and signs) [ Time Frame: from 5th to 9th day ]; [ Time Frame: from 10th to 14th day ] | |
In the report Increase discharge from outpatient care with COVID-19 mild disease | |
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 pre-print article, the retrospective study registry was used in data extraction and risk of bias assessment. Protocol or statistical analysis plan were not available. Sample size calculation was presented and target number enrolled was achieved. Number or size of clusters were not reported; results were reported for individuals, not clusters. The study included mild outpatients and the main outcomes were symptoms and discharge from outpatient care, harms/adverse events were not reported. |
Trial NCT04739410
Publication Khan Chachar AZ, Int J Sci (2020) (published paper)
Funding: No specific funding
Conflict of interest: *
Methods | |
RCT Blinding: Unblinded | |
Location :
Single center / Pakistan Follow-up duration (days): 7 | |
Inclusion criteria |
|
Exclusion criteria |
|
Interventions | |
Treatment
Ivermectin 12mg PO followed by 12 mg after 12 hours and 12mg after 24 hours |
|
Control
Standard care | |
Participants | |
Randomized participants : Ivermectin=25 Standard care=25 | |
Characteristics of participants N= 50 Mean age : NR 31 males Severity : Mild: n= 50/ Asymptomatic: n=0 | |
Primary outcome | |
In the register 1.Resolution of symptoms [ Time Frame: 7 days ] Will look for resolution of Fever, Fatigue, myalgias, cough and we had an questionaire for that as well and followed up on their chest x rays for progression of the disease Progression of the disease [ Time Frame: 14 days ] did the disease progress from mild to moderate severity, like follow up chest x ray showed more infiltrates or their oxygen saturations in % dropped from their baseline and baseline symptoms persisted and got worse | |
In the report Improvement of symptoms like Fever, Cough, sore throat, Headache, Shortness of breath, lethargy, and fatigue at day 7. | |
Documents avalaible |
Protocol Yes. In English Statistical plan Yes 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 |
High |
General comment |
In addition to all available versions of the published/pre-print article, the study registry and protocol were used in data extraction and risk of bias assessment. The target sample size specified in the registry was achieved.There is no change from the trial registration in the intervention. The outcome "Progression of the disease [ Time Frame: 14 days ]" was mentioned in the register but not reported.
This study was updated on February 9th, 2021 after contact with authors. |
Trial NCT04405843
Publication Lopez-Medina E, JAMA (2021) (published paper)
Dates: 2020-07-15 to 2020-11-30
Funding: Mixed (Centro de Estudios en Infectologia Pediatrica; Tecnoquimicas (drug and placebo donation))
Conflict of interest: Yes
Methods | |
RCT Blinding: Participants, outcome assessor and health care pro | |
Location :
Single center / Colombia Follow-up duration (days): 21 | |
Inclusion criteria |
|
Exclusion criteria |
|
Interventions | |
Treatment
Ivermectin 300 mcg/kg/day orally for 5 days |
|
Control
Placebo | |
Participants | |
Randomized participants : Ivermectin=238 Placebo=238 | |
Characteristics of participants N= 476 Mean age : NR 167 males Severity : Mild: n= 394/ Asymptomatic: n=0 | |
Primary outcome | |
In the register Time until resolution of symptoms [ Time Frame: 21 days ] | |
In the report Time from randomization to complete resolution of symptoms within the 21-day follow-up period | |
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 study protocol, statistical analysis plan and trial registry were used in data extraction and assessment of risk of bias. The original primary outcome measure (worsening by 2 points in an 8-point ordinal scale) was changed to resolution of symptoms during the trial due to low incidence of the original outcome, resulting an unattainable sample size. This change was identified before the interim analysis and approved by the data and safety monitoring board.
Other than that there were no substantive differences between the published article and the study protocol, statistical analysis plan and trial registry. For two weeks both arms received Ivermectin due to a labeling error, including 38 in the control group; all patients recruited during this period (n=75) were not included in primary analyses extracted here, but were included in sensitivity and as-treated analysis. Quote: "On October 20, 2020, the lead pharmacist observed that a labeling error had occurred between September 29 and October 15, 2020, resulting in all patients receiving ivermectin and none receiving placebo during this time frame. The study blind was not unmasked due to this error. The data and safety monitoring board recommended excluding these patients from the primary analysis but retaining them for sensitivity analysis. The protocol was amended to replace these patients to retain the originally calculated study power. The primary analysis population included patients who were analyzed according to their randomization group, but excluded patients recruited between September 29 and October 15, 2020, as well as patients who were randomized but later found to be in violation of selection criteria. Patients were analyzed according to the treatment they received in the as-treated population (sensitivity analysis)." This study was updated on May 19th, 2021 with data gained from contact with authors. |
Trial *
Publication Podder C, IMC J Med Sci (2020) (published paper)
Dates: 2020-05-01 to 2020-07-31
Funding: No specific funding (Self-financed)
Conflict of interest: No
Methods | |
RCT Blinding: Unblinded | |
Location :
Single center / Bangladesh Follow-up duration (days): 10 | |
Inclusion criteria |
|
Exclusion criteria |
|
Interventions | |
Treatment
Ivermectin |
|
Control
Standard care | |
Participants | |
Randomized NR Analyzed 62 participants Ivermectin=32 Standard care=30 | |
Characteristics of participants N= 62 Mean age : NR 44 males Severity : Mild: n= 62/ Asymptomatic: n=0 | |
Primary outcome | |
In the register NR | |
In the report Time needed for resolution of fever, cough, shortness of breath and finally, full recovery from all symptoms and the negative result of repeat RT-PCR on day 10. | |
Documents avalaible |
Protocol NR Statistical plan NR 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 |
High |
General comment | Only the published article was used in data extraction and risk of bias assessment as no study registry, protocol or analysis plan was available. No a priori sample size determination was reported. The randomized proportion of participants per group was not reported. Patients were allocated to treatment groups using a quasi-randomisation method, based on odd and even registration numbers in a consecutive fashion. After allocation, a sizeable proportion of patients was not included in the analysis due to the prior duration of symptoms and it is unclear whether this was a post hoc decision. |
Trial NCT04529525
Publication IVERCOR-COVID19 - Vallejos J, BMC Infect Dis (2021) (published paper)
Dates: 2020-08-19 to 2021-02-22
Funding: No specific funding (None)
Conflict of interest: No
Methods | |
RCT Blinding: double blinding | |
Location :
Single center / Argentina Follow-up duration (days): 42 | |
Inclusion criteria |
|
Exclusion criteria |
|
Interventions | |
Treatment
Ivermectin Dose staggered by weight: Initial dose: 12 mg (<80 Kg), 18 mg (80-110 kg), or 24 mg (>110 kg) orally first day Maintenance dose: 12 mg (<80 Kg), 18 mg (80-110 kg), or 24 mg (>110 kg) orally once a day for 2 days |
|
Control
Placebo | |
Participants | |
Randomized participants : Ivermectin=250 Placebo=251 | |
Characteristics of participants N= 501 Mean age : NR 264 males Severity : Mild: n= 501/ Asymptomatic: n=20 | |
Primary outcome | |
In the register Percentage of Hospitalization of medical cause in patients with COVID-19 in each arm [ Time Frame: through study completion, an average of 30 days ] | |
In the report Hospitalization for any reason of patients with COVID-19 | |
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 |
Low |
General comment |
In addition to the published article with supplementary materials, the study registry and protocol were used in data extraction and risk of bias assessment. The study achieved the target sample size specified in the trial registry. There is no change from the trial registration in the intervention and control treatments. The primary outcome indicated in registry reflects the primary outcome reported in the paper. Time to death and time to WHO score 7 and above was based on a 12 (+-3) days follow up.
On 30th July, 2021, we received additional information from authors on this study. This study was updated with data from contact with authors and the published report on August 16th, 2021. |