Tenofovir + Emtricitabine vs Standard care (RCT)

Mild outpatients

FOREST PLOTS -2022-11-18

Studies description

Trial NCT04712357
Publication Arruda EAG, medRxiv (2021) (preprint)
Dates: 2020-11-09 to 2021-07-05
Funding: Public/non profit (Rede Virus, Ministerio da science, Tecnology, Inovation e Comunication (MCTIC), Brasilia-DF through CNPq)
Conflict of interest: No

Methods
RCT
Blinding: double blinding
Location : Single center / Brazil
Follow-up duration (days): 28
Inclusion criteria
  • Age between 18-60 years
  • Clinical suspicion of mild to moderate COVID-19 respiratory infection. Mild to moderate respiratory infection was defined as absence of dyspnea, respiratory distress and O2 saturation < 95%
Exclusion criteria
  • The patient was already receiving some study drug
  • Plan for hospitalization within the next 24 hours
  • Contraindication for the use of study drugs
  • Diagnosis of HIV and/or hepatitis B virus infections
  • Pregnant woman
  • Patient with fixed residence outside the study municipality
Interventions
Treatment
Tenofovir
300 mg Tenofivir orally once a day for 10 days

TDF+FTC
300 mg Tenofivir + 200 mg Emtricitabine orally once a day for 10 days
Control
Placebo

Participants
Randomized
participants :
Placebo=47
Tenofovir=47
TDF+FTC=45
Characteristics of participants
N= 139
Mean age : NR
0 males
Severity : Mild: n= 139/ Asymptomatic: n=0
Primary outcome
In the register
The time to recovery, defined at day 7 days follow up after enrollment, on which a patient met the criteria for category 1, 2, or 3 on the eight-category ordinal scale. [ Time Frame: Day 7 follow up after enrollment. ] The categories are as follows: 1 - No signals and symptoms; 2 - One signal or symptom; 3 - Two signals or symptoms; 4 - Three or more signals or symptoms; 5 - Hospitalized, no active medical problems; 6 - Hospitalized, not on oxygen; 7 - Hospitalized, on oxygen; and 8 - Hospitalized, on high flow oxygen.
In the report
The score of symptoms and predictive signs of COVID-19, assessed on the seventh day of patient follow-up / Two scores based on these symptoms (Table 4) were delineated as primary parameters and most associated with SARS-CoV-2 infection to assess efficacy of TDF and TDF combined with FTC in patients on the seventh day of COVID-19 evolution.
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 pre-print article, the trial registry was used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. The trial was registered retrospectively. The primary outcomes in the article only partially reflect that in the registry. Several outcome time points in the registry are not reported. The trial (n = 227) achieved its target sample size (n = 219). However, the trial enrolled patients with suspected COVID-19, of whom only 139 were subsequently found to be COVID patients, and the extracted outcomes were reported only for these patients.

Trial NCT04685512; EuraCT 2020-001867-94
Publication Parientia JJ, EClinicalMedicine (2021) (published paper)
Dates: 2020-11-20 to 2021-03-19
Funding: Public/non profit (Caen University Hospital)
Conflict of interest: Yes

Methods
RCT
Blinding: Unblinded
Location : Multicenter / France
Follow-up duration (days): 14
Inclusion criteria
  • SARS CoV-2 infected adults confirmed by nasopharyngeal swab RT-PCR test
  • symptoms of COVID-19 for less than 7 days before enrollment
  • did not require immediate hospitalization.
Exclusion criteria
  • breastfeeding
  • positive pregnancy test
  • estimated glomerular filtration rate <80 mL/min per 1.73 m2, as requested by the ANSM
  • living with HIV
  • hepatitis B
  • hepatitis C
  • contraindication to use the experimental drugs
  • capillary oximetry less than 95%
  • clinical evaluation by investigators leading to hospitalisation
  • use of non-steroid antiinflammatory or any nephrotoxic drugs during the past 7 days.
Interventions
Treatment
TDF+FTC
Initial dose: TDF 490 mg/day + FTC 400 mg/day on day 1; Maintenance dose: TDF 245 mg/day + FTC 200 mg/day on days 2-7 orally.
Control
Standard care

Participants
Randomized
participants :
TDF+FTC=30
Standard care=30
Characteristics of participants
N= 60
Mean age : NR
26 males
Severity : Mild: n= 60/ Asymptomatic: n=0
Primary outcome
In the register
Reduction of SARS-CoV2 viral load assessed by Ct PCR at day-4 adjusted on Ct PCR SARS-CoV2 viral load at baseline (ANCOVA) [ Time Frame: Day-4 after the start of study ]
In the report
variation of SARS-CoV2 viral load burden from baseline assessed by the variation of the number of cycle thresholds (Ct) of RT-PCR from nasopharyngeal samples at day-4 compared to baseline.
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 preprint, the study registry was used in data extraction and risk of bias assessment. 5% of included outpatients were reported to have moderate COVID-19 at baseline (but were outpatients). There are no substantive changes from the registry in the study population, procedures, outcomes, intervention and control treatments. 10% of intervention participants discontinued treatment due to adverse events. Unblinded study. Total adverse events are not reported. The study achieved the target sample size specified in the trial registry.