Trial NCT04402866; EudraCT 2020-001807-18
Publication Singh D, 2021 (preprint)
Funding: Private (Theravance Biopharma Ireland Limited ; Theravance Biopharma US, Inc.)
Conflict of interest: Yes
| Methods | |
| RCT Blinding: double blinding | |
| Location :
Multicenter / Moldova, UK, Ukraine Follow-up duration (days): 28 | |
| Inclusion criteria | 18 to 80 years of age ; PCR-confirmed symptomatic COVID-19 (symptoms for 3â14 days) ; hospitalised and required supplemental oxygen to maintain saturation >90% ; informed consent. |
| Exclusion criteria | - Currently receiving invasive mechanical ventilation ;
- Presence or suspicion of active malignancy with the exception of cancer in situ (e.g., skin cancer) ; - Evidence of serious active infection other than COVID-19 ; - Current dia |
| Interventions | |
| Treatment 1 TD-0903 1 mg | |
| Control Placebo | |
| Control TD-0903 3 mg | |
| Control TD-0903 10 mg | |
| Participants | |
| Randomized 25 participants n1=6/ n2=6/ n3=7/ n4=6/ | |
| Characteristics of participants N=25 Mean age : 57.3 17 males Severity : Mild: n=0 / Moderate: n=25/ Severe: n=0 Critical: n=0 | |
| Primary outcome | |
| In the register Safety (Change from baseline in vital signs and clinical laboratory results; Incidence and severity of treatment-emergent AEs through Day 7 & 28), Pharmacokinetics (Plasma PK parameters on Day 1 and Day 7), Pharmacodynamics (Change from baseline in SaO2/FiO2 ratio through Day 7) | |
| In the report Safety and tolerability, pharmacokinetics, and oxygen saturation/fraction of inspired oxygen ratio; clinical outcomes were also explored | |
| Documents available |
Protocol NR Statistical plan NR Data-sharing stated No |
| 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, two prospective trial registries were used in data extraction and assessment of risk of bias. Neither study protocol nor statistical analysis plan was available. The article reports on the completed part 1 of a 2-part Phase 2 trial. The small sample size of this early phase clinical trial limited evaluation of clinical efficacy through between-group comparisons and formal control for potential confounders (a sample size of 8 patients per study arm was deemed appropriate to assess TD--0903 safety and tolerability during dose escalation). Of note, one patient receiving TD-0903 3 mg was discontinued due to a negative SARS-CoV-2 PCR screening test returned after randomisation; per protocol, this subject was replaced. No outcomes for part 1 were specified in one registry, while there were several differences between the outcomes in the other registry and those reported in the pre-print article. Neither registry contained information on intervention dosing or schedule. The study achieved its pre-stated target sample size. |