. 2022 Feb 26;10(2):e00925. doi: 10.1002/prp2.925

TABLE 4.

Summary of findings: Naproxen compared to Placebo/Other NSAIDs for ARTI

Patient or population: ARTI Intervention: Naproxen Comparison: Placebo/Other NSAIDs
Fever № of participants: 79 (1 RCT)	RR 0.1368 (0.0315 to 0.5936)	4.1%	0.6% (0.1 to 2.5)	3.6% fewer (4 fewer to 1.7 fewer)	⨁⨁⨁⨁ HIGH ^a	Naproxen results in a reduction in fever.
Cough № of participants: 79 (1 RCT)	–	The mean cough was 0	–	MD 0.8 lower (1.8 lower to 0.17 higher)	⨁⨁⨁◯ MODERATE ^b	Naproxen results in little to no difference in cough compared with placebo.
Sore Throat № of participants: 79 (1 RCT)	–	The mean sore Throat was 0	–	MD 0.5 lower (1.9 lower to 0.93 higher)	⨁⨁⨁◯ MODERATE ^b	Naproxen probably results in little to no difference in sore Throat.
ARDS № of participants: 217 (1 RCT)	RR 0.5266 (0.3345 to 0.8288)	37.3%	19.6% (12.5 to 30.9)	17.6% fewer (24.8 fewer to 6.4 fewer)	⨁⨁◯◯ LOW ^c	Naproxen may result in a reduction in ARDS.
Mortality № of participants: 217 (1 RCT)	RR 0.1142 (0.0147 to 0.8862)	8.2%	0.9% (0.1 to 7.3)	7.2% fewer (8.1 fewer to 0.9 fewer)	⨁⨁⨁◯ MODERATE ^d	Combination of Naproxen + Clarithromycin may result in a reduction in mortality. 1/107 compared with 9/110 were deceased in a trial of Naproxen + Clarithromycin + Oseltamivir versus Oseltamivir alone in H3N2 influenza patients followed for 30 days.
GI Adverse Events № of participants: 103 (2 RCTs)	not pooled	10.4%	not pooled	not pooled	⨁⨁◯◯ LOW ^e	The effect of Naproxen in GI upset is uncertain. Salmon Rodriguez et al. in a pediatrics population‐although imprecise‐ reports inferior tolerability compared with Nimesulide.

Patient or population: ARTI

Intervention: Naproxen

Comparison: Placebo/Other NSAIDs

Outcome

№ of participants

(studies)

Relative effect

(95% CI)

Anticipated absolute effects (95% CI)

Certainty

What happens

Difference

Fever

№ of participants: 79

(1 RCT)

RR 0.1368

(0.0315 to 0.5936)

4.1%

0.6%

(0.1 to 2.5)

3.6% fewer

(4 fewer to 1.7 fewer)

⨁⨁⨁⨁

HIGH ^a

Naproxen results in a reduction in fever.

Cough

№ of participants: 79

(1 RCT)

–

The mean cough was 0

–

MD 0.8 lower

(1.8 lower to 0.17 higher)

⨁⨁⨁◯

MODERATE ^b

Naproxen results in little to no difference in cough compared with placebo.

Sore Throat

№ of participants: 79

(1 RCT)

–

The mean sore Throat was 0

–

MD 0.5 lower

(1.9 lower to 0.93 higher)

⨁⨁⨁◯

MODERATE ^b

Naproxen probably results in little to no difference in sore Throat.

ARDS

№ of participants: 217

(1 RCT)

RR 0.5266

(0.3345 to 0.8288)

37.3%

19.6%

(12.5 to 30.9)

17.6% fewer

(24.8 fewer to 6.4 fewer)

⨁⨁◯◯

LOW ^c

Naproxen may result in a reduction in ARDS.

Mortality

№ of participants: 217

(1 RCT)

RR 0.1142

(0.0147 to 0.8862)

8.2%

0.9%

(0.1 to 7.3)

7.2% fewer

(8.1 fewer to 0.9 fewer)

⨁⨁⨁◯

MODERATE ^d

Combination of Naproxen + Clarithromycin may result in a reduction in mortality. 1/107 compared with 9/110 were deceased in a trial of Naproxen + Clarithromycin + Oseltamivir versus Oseltamivir alone in H3N2 influenza patients followed for 30 days.

GI Adverse Events

№ of participants: 103

(2 RCTs)

not pooled

10.4%

not pooled

⨁⨁◯◯

LOW ^e

The effect of Naproxen in GI upset is uncertain. Salmon Rodriguez et al. in a pediatrics population‐although imprecise‐ reports inferior tolerability compared with Nimesulide.

GRADE Working Group grades of evidence:

High certainty: We are very confident that the true effect lies close to that of the estimate of the effect

Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different

Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect

Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Explanations: a. fever in this study is not reported as mean temperature. A 4‐score subjective scale and consecutive dichotomous temperature measurement are reported; b. The total number of participants is below 100; c. Surrogate outcomes are used for ARDS. a co‐intervention of clarithromycin was used along with naproxen; d. A co‐intervention of clarithromycin was used along with naproxen and e. Effect estimates in 3 studies demonstrate a wide confidence interval; this could be due to a sample size of less than 100 patients per trial. Also, effect estimates are not consistent in larger trials.

Abbreviations: CI, Confidence interval; MD, Mean difference; RR, Risk ratio.

The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).