Background
This summary has been developed to facilitate the organization and conduct of clinical research during the current nCoV outbreak. It is not intended to be directive, but rather to articulate scientific and logistical issues during a response that has engaged a large number of researchers whose expertise varies, and who are working to very tight timelines.
Scientific Knowledge Gaps: Interventions
1. What is the clinical phenotype of nCoV infection?
- What are the predominant signs and symptoms
- Over what period of time do they evolve
- What percentage of patients develop mild (ambulatory), moderate (hospitalized with minimal support), and severe (cared for in a monitored area or ICU) disease
- Over what period of time does progression from mild to severe disease occur
- What are the patient risk factors for severe disease
- What is the mortality rate for severe disease
- Can the virus be transmitted by asymptomatic patients
This information can be captured quickly, and is probably best recorded through the ISARIC clinical characterization protocol (https://isaric.tghn.org/novel-coronavirus/). Are there other registries that should be recommended?
Rapid REB approval for data collection and sharing is necessary.
2. What are the most effective interventions to accelerate viral clearance?
- Available and novel anti-viral agents
- Monoclonal or polyclonal antibodies
- Convalescent plasma
- Traditional Chinese medicine
This question is being addressed by the antiviral working group, and a compendium of options has been developed. Prioritization is needed.
3. What adjuvant therapies targeting the host response are most promising?
- Interferons (which)
- IL-1ra
- Corticosteroids
- Vitamin C
- Heparin
- Statins
- ACE inhibitors
- Others?
4. What strategies involving supportive interventions have the greatest probability of improving outcomes in severe infection?
- Novel ventilation strategies
- ECMO
- Fluid minimization
- Reduced oxygenation targets
These are likely to be the least important research themes, given that impact is likely small. But they are also readily included as part of a platform trial.
Study Population
5. Which populations should be targeted, and with what objectives (see later):
- Mild-moderate disease
i. Accelerate viral clearance
ii. Accelerate symptom resolution
iii. Prevent progression to severe disease
- Severe disease
i. Accelerate resolution of need for supportive care and hospitalization
ii. Improve survival
iii. Minimize long term sequelae
- Post-exposure prophylaxis
i. Prevent disease development
- Can an intervention be studied in both mild and severe disease
i. Anti-virals relevant to both
ii. A trial outcome measure that tracked progression could work across populations
iii. Principle challenges likely to be organizational – different research teams and approaches on wards vs ICUs, and need for different consent models
Endpoints for Clinical Trials
6. Should there be a common primary outcome measure across trials, and if so, what should it be
- Comprehensive Recovery Scale (based on severity and progress through health care system (see Appendix A)
- Mortality
- Duration of hospitalization
- Viral load
- Other
7. What are key secondary outcomes to record, and should these be standardized
- Mortality at varying time points
- Biomarkers
- Viral load
- Symptom resolution
- Organ dysfunction evolution/resolution
- Duration of hospital stay
- Duration of ICU stay
- Late sequelae – days home, quality of life
- Costs
- Other
Facilitating a rapid research response
8. How can existing resources best be harnessed to activate a research response
- REMAP-CAP – adoption of the pandemic response protocol in recruiting sites
- ISARIC member groups
- InFACT – engagement of three dozen member groups on every continent
i. Opportunities for use of REMAP-CAP platform to engage sites in Southeast Asia, China, Africa, Central and South America
- Other clinical research networks – identifying capacity, reach and resources
本网站内容转载须联系版权方授权。
