Trial NCT04402866
Publication NCT04402866, Unpublished (2022) (results posted on registry)
Funding: Not reported/unclear
Conflict of interest: *
Methods | |
RCT Blinding: triple blinding | |
Location :
Multicenter / Brazil, Finland, Moldova, Romania, Ukraine, UK, USA Follow-up duration (days): 28 | |
Inclusion criteria |
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Exclusion criteria |
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Interventions | |
Treatment
TD-0903 Loading dose: 6 mg by oral inhalation on Day 1. Maintenance dose: 3 mg by oral inhalation once daily for up to 7 days. |
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Control
Placebo | |
Participants | |
Randomized participants : TD-0903 =106 Placebo=104 | |
Characteristics of participants N= 210 Mean age : NR 128 males Severity : Mild: n=0 / Moderate: n=* / Severe: n=* Critical: n=0 | |
Primary outcome | |
In the register Number of Respiratory Failure-free Days (RFDs) From Randomization to Day 28 [ Time Frame: Randomization to Day 28 ] An RFD was defined as a day that a participant was alive and did not require the use of any respiratory support (invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow oxygen devices, or oxygen supplementation) from randomization through Day 28. The number of RFDs was 0 for participants who used respiratory support for 28 days or longer or for participants who died on or before Day 28. A clinical status score of ≤ 4 on a given day was equivalent to an RFD. The clinical status categories and associated scores ranged from 1-8 where a higher score represented a worse outcome. A clinical status score of 4 was defined as a participant who was hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (whether or not related to COVID-19). | |
In the report NR | |
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 |
Some concerns |
General comment | This is an unpublished trial whose results have been reported in ClinicalTrials.gov. The trial registry, protocol and statistical analysis plan were used in data extraction and assessment of risk of bias. The trial was registered prospectively. The study achieved its target sample size (N-198). The proportion of subjects in each category of the Clinical Status scale (6 scores) outcome was modified into the 8 scores WHO ordinal scale retrospectively. Some outcomes (e.g.adverse events and serious adverse events) are reported, but were not pre-specified in the registry. These results report on Part 2 of a 2-part Phase 2 trial. |
Trial NCT04402866; EudraCT 2020-001807-18
Publication Singh D, medRxiv (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 |
|
Exclusion criteria |
|
Interventions | |
Treatment
TD-0903 1 mg Initial dose: 2 mg/day via inhalation for the first 24 hours-Maintenance dose: 1 mg/day via inhalation for up to 7 days. TD-0903 Initial dose: 6 mg/day via inhalation for the first 24 hours-Maintenance dose: 3 mg/day via inhalation for up to 7 days. TD-0903 10 mg 10 mg/day via inhalation for up to 7 days. |
|
Control
Placebo | |
Participants | |
Randomized participants : TD-0903 1 mg=6 TD-0903=7 TD-0903 10 mg=6 Placebo=6 | |
Characteristics of participants N= 25 Mean age : NR 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 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, the protocol and the statistical analysis plan were used in data extraction and assessment of risk of bias.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. The study achieved its pre-stated target sample size.
This study was updated on September 28th, 2022 with data extracted from the registry. |