Table 3.
Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence profile for population, intervention, comparison, outcome 18: Nirmatrelvir/ritonavir for mild or moderate coronavirus disease 2019a
| People: Adult, unvaccinated patients with mild-to-moderate symptomatic COVID-19 and one or more risk factorsb for disease progression within 5 d of the onset of symptoms (pregnant and breast-feeding patients excluded). Settings: Ambulatory patients not requiring oxygen, 330 centres in 21 countries. Intervention: Nirmatrelvir/ritonavir at 300/100 mg administered orally, twice daily for 5 d. Comparison: Placebo | |||||
|---|---|---|---|---|---|
| Outcomes | Absolute effect |
Relative effect (95% CI) | Number of studies | Certainty of the evidence (GRADE) | |
| Without nirmatrelvir/ritonavir | With nirmatrelvir/ritonavir | ||||
| Hospitalisation or death D 28, ≤5 d symptom onset |
63 per 1000 | 8 per 1000 | RR: 0.12 (0.06–0.25) | 1 [31] (2085 patients) | ⊕⊕⊕⊖ Moderate (serious imprecision) |
| Difference: 55 fewer per 1000 (95% CI: 59 fewer to 47 fewer) | |||||
| All-cause mortality D 28, ≤5 d from the onset of symptoms |
11 per 1000 | 0 per 1000 | RR: 0.04 (0.00–0.68) | 1 [31] (2085 patients) | ⊕⊕⊖⊖ Low (very serious imprecision) |
| Difference: 11 fewer per 1000 (95% CI: 11 fewer to 4 fewer) | |||||
| Hospitalisation D 28, ≤5 d from the onset of symptoms |
62 per 1000 | 7 per 1000 | RR 0.12 (0.06–0.26) | 1 [31] (2085 patients) | ⊕⊕⊕⊖ Moderate (serious imprecision) |
| Difference: 55 fewer per 1000 (95% CI: 58 fewer to 46 fewer) | |||||
| Adverse events within 28 d of commencing treatment | 239 per 1000 | 227 per 1000 | RR: 0.95 (0.82–1.10) | 1 [31] (2224 patients) | ⊕⊕⊕⊖ Moderate (serious imprecision) |
| Difference: 12 fewer per 1000 (95% CI: 43 fewer to 24 more) | |||||
| Serious adverse events within 28 d of commencing treatment | 66 per 1000 | 16 per 1000 | RR: 0.24 (0.15–0.41) | 1 [31] (2224 patients) | ⊕⊕⊕⊖ Moderate (serious imprecision) |
| Difference: 50 fewer per 1000 (95% CI: 56 fewer to 39 fewer) | |||||
| Discontinued because of adverse events within 28 d of commencing treatment | 42 per 1000 | 21 per 1000 | RR: 0.49 (0.30–0.81) | 1 [31] (2224 patients) | ⊕⊕⊕⊖ Moderate (serious imprecision) |
| Difference: 21 fewer per 1000 (95% CI: 29 fewer to 8 fewer) | |||||
COVID-19, coronavirus disease 2019; GRADE, Grading of Recommendations Assessment, Development and Evaluation; RR, risk ratio.
aEvidence adopted: Australian Guideline for clinical care of patients with COVID-19 at https://app.magicapp.org/#/guideline/6268/section/101966 accessed March–April 2022.
bRisk factors for disease progression: ≥60 years of age; body mass index >25 kg/m2; cigarette smoking; immuno-suppressive disease (including human immuno-deficiency virus infection with a CD4 cell count of <200 mm3) or prolonged iatrogenic immunosuppression; chronic lung, cardiovascular, kidney, or sickle cell disease; hypertension; diabetes; cancer; neurodevelopmental disorders or other medically complex conditions or medical-related technological dependence.