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

TABLE 1.

Study characteristics

NSAID	Study	Participants age & setting	Intervention (number of participants)	Comparison (number of participants)	Outcomes
Ibuprofen	Llor, C. 2013 Spain	Adult Inpatient ARTI	Ibuprofen 600 mg TDS For 10 days (n = 136)	Placebo (n = 143)		Number of days with cough Mean difference (95% CI^d)				GI upset RR (95% CI)

2 1.5 to 2.5	1.84 0.55 to 6.15

Bernard, G. R. 1997 North America	Adult Inpatient Sepsis Criteria	Ibuprofen IV/inf./ 10 mg/kg QID (maximal dose: 800 mg daily) for 2 days (n = 224)	Placebo (n = 231)	4 h Fever Mean difference (95% CI)			24 h Minute‐Ventilation (L/min) Mean difference (95% CI)	30‐day Mortality RR (95% CI)	GI Bleeding RR (95% CI)

−0.80 −0.78 to −0.82	0.92 0.85 to 0.99	0.88 0.70 to 1.11	0.58 0.26 to 1.29

Bouroubi, A. 2017 Europe	Adult Outpatient Sore Throat	Ibuprofen 25mg lozenge p.o. up to 6 doses daily for 4 days (n = 194)	Placebo lozenges p.o. for 4 days (n = 191)			4th day pain Relieved RR (95% CI)			GI upset RR (95% CI)

1.51 1.06 to 2.15	2.95 0.60 to 14.45

Little, P. 2013 United Kingdom	Adult & Pediatrics Outpatient ARTI	Ibuprofen 200–400 mg p.o. QID for 3 days (n = 150)	Paracetamol 15 mg/kg p.o. QID for 3 days (n = 152)						GI upset RR (95% CI)

0.83 0.63 to 1.10

Winther, B. 2001 Denmark	Adult Outpatient URTI	Ibuprofen 400 mg p.o. TDS for 3 days (n = 38)	Placebo (n = 42)	Chilliness improvement 3‐day (0–9 score) Mean difference (95% CI)	Cough improvement 3‐day (0–9 score) Mean difference (95% CI)	Sore Throat improvement 3‐day (0–9 score) Mean difference (95% CI)

0.63 0.75 to 0.51	0.83 1.05 to 0.61	0.31 0.48 to 0.14

Gwaltney, J. M., Jr. 2002 USA	Adult Outpatient Rhinovirus Inoculation	Intranasal placebo + oral chlorpheniramine (12 mg extended release) and Tab. Ibuprofen 400 mg BD for 5 days (n = 61)	Intranasal and oral placebos (n = 30)		3rd day Cough (0–4 score) Mean difference (95% CI)	3rd day Sore throat (0–4 score) Mean difference (95% CI)

−0.12 −0.09 to −0.15	−0.24 −0.20 to −0.28

Sperber, S. J. 1989 USA	Adult Outpatient Rhinovirus Inoculation	Pseudoephedrine HC1 60 mg + Ibuprofen 200 mg p.o. for 5 days (n = 23)	Pseudoephedrine HC1 60 mg + placebo p.o. for 5 days (n = 23)			Sore Throat (0–18 score) Mean difference (95% CI)			GI upset RR (95% CI)

−1 −3.10 to 1.10	0.33 0.01 to 7.78

Kim, C‐K. 2013 South Korea	Pediatric Outpatient URTI	Dexibuprofen 3.5 or 7 mg/kg p.o. single dose (n = 75)	Ibuprofen 5 or 10 mg/kg p.o. single dose (n = 76)	4 h Fever Mean difference (95% CI)					GI upset RR (95% CI)

0.26 −0.0232 to 0.5432	0.98 0.70 to 1.39

Hay AD. 2008 United Kingdom	Pediatric Outpatient Fever	Ibuprofen 10 mg/kg p.o. q6–8hr for 2 days (n = 52)	Paracetamol 15 mg/kg p.o. q4–6hr for 2 days (n = 52)	Time until first fever clearance (minutes) Mean difference (95% CI)				2nd day Recovered child RR (95% CI)	GI upset RR (95% CI)

28.8 7.68 to 49.92	0.97 0.52 to 1.80

2nd day temperature Mean difference (95% CI)	5th day Recovered child RR (95% CI)	0.75 0.39 to 1.43

0 −0.34 to 0.34	0.83 0.49 to 1.38

Yoon, J. S. 2008 South Korea	Pediatric Outpatient URTI	Ibuprofen 10 mg/kg p.o. single dose (n = 85)	Dexibuprofen 5 mg/kg p.o. single dose (n = 86)	6 h Fever Reduction Mean difference (95% CI)					GI upset RR (95% CI)

−0.1 ‐0.39 to 0.19

6 h Fever reduced to normal RR (95% CI)	1.01 0.37 to 2.76

1.40 0.96 to 2.03

Ulukol, B. 1999 Turkey	Pediatric Outpatient URTI	Ibuprofen (suspension) 10 mg/kg p.o. TDS + Anti‐Biotics for 5 days (n = 30)	Paracetamol (suspension) 10 mg/kg p.o. TDS + Anti‐Biotics (n = 30)	Fever improved 2nd day RR (95% CI)	Cough improved 5th day RR (95% CI)

0.60 0.33 to 1.12	0.79 0.60 to 1.06

Bertin, L. 1991 France	Pediatric Outpatient Sore Throat	Ibuprofen 10 mg/kg p.o. TDS + penicillin for 7 days (n = 77)	Placebo + penicillin for 7 days (n = 76)			2nd day pain relief RR (95% CI)			GI upset RR (95% CI)

1.68 1.27 to 2.23	0.99 0.30 to 3.27
Naproxen	Hung 2017 Hong Kong	(H3N2) influenza inpatient Adult	clarithromycin 500 mg, naproxen 200mg, and oseltamivir 75 mg BD for 2 days, followed by 3 days of oseltamivir 75 mg BD (n = 107)	oseltamivir 75 mg BD for 5 days (n = 110)				Respiratory support during hospitalization RR (95% CI)	Days of Acute care hospitalization median (1st to 3rd quartile)
0.53 0.33 to 0.83	2 (1–3)	3 (2–4)
HDU admission required during hospitalization RR (95% CI)	30‐day mortality RR (95% CI)
0.51 0.31 to 0.86	0.11 0.01 to 0.89
ICU^h admission required during hospitalization RR (95% CI)	90‐day mortality RR (95% CI)
0.29 0.06 to 1.38	0.19 0.04 to 0.82
Sperber, S. J. 1992 USA	Outpatient Adults Viral inoculation with RSV	Naproxen 400 mg or 500 mg p.o. stat followed by 200 mg or 500 mg TDS for 5 days (n = 39)	Placebo (n = 40)	5th day Chilliness (0–4 score) Mean difference (95% CI)	5th day Cough (0–4 score) Mean difference (95% CI)	5th day Sore throat (0–4 score) Mean difference (95% CI)			GI Upset RR (95% CI)
0.40 −0.11 to 0.91
Fever developed (Temp. >37.5) RR (95% CI)	0.8 −0.17 to 1.80	0.5 −0.93 to 1.90	0.53 0.05 to 5.57
0.14 0.03 to 0.59

Gwaltney, J. M., Jr. 1992 USA	Outpatient Adults Viral inoculation with RSV	‐Naproxen 500 mg stat and then 250 mg TDS ‐Ipratropium 80 mcg (2 puffs/ nostril) TDS ‐IFN‐a2b 3 million units (0.1 mL/nostril) TDS for 4 days (n = 16)	Placebo (n = 8)						GI Upset RR (95% CI)

1.59 0.07 to 35.15

Salmon Rodriguez, L. E. 1993 Mexico	(Probably inpatient) Pediatrics Sore Throat	Naproxen TDS p.o. for 8 days Dosing: (25 mg per ml): −2.5 ml for 1 to 3 years. −5 ml for 4 to7 years. −7.5 ml for 8 to 10 years. (n = 50)	Nimesulide BD p.o. for 8 days Dosing: (l0 mg per ml): ‐ 2.5 ml for 1 to 3 years. ‐ 5 ml for 4to 7 years. ‐ 7.5 ml for 8 to 10 years. ‐ 10 ml for more than 10 years. (n = 49)						GI Upset RR (95% CI)

2.73 0.95 to 7.89
Diclofenac	Grebe 2003 Germany	Adult Outpatient Influenza‐like symptoms	Diclofenac 25mg p.o. daily For 3 days (n = 121)	Placebo (n = 115)	6 h Fever under 37.8˚C RR (95% CI)					GI Upset RR (95% CI)
2.73 1.27 to 5.86	0.48 0.043 to 5.17
Weckx 2002 Brazil/ Columbia/ Mexico	Adult Outpatient Influenza‐like symptoms	Diclofenac 75 mg p.o. BD for 5 days (n = 101)	celecoxib 200 mg p.o. BD for 5 days (n = 107)			3rd day Visual Analogue Scale (100 points) Mean difference (95% CI)			GI Upset RR (95% CI)
2.14 1.56 to 2.72	2.14 0.68 to 6.76
Bettini 1986 Italy	Adult Outpatient Influenza‐like symptoms	Diclofenac 25 mg p.o. BD For 2 days (n = 60)	500 mg Aspirin p.o. TDS for 2 days (n = 60)	6 h Fever Mean Difference (95% CI)		2nd day sore throat moderate symptom reduction RR (95% CI)			GI Upset RR (95% CI)
0.9 0.5 to 1.3	0.99 0.77 to 1.28	0.2 0.02 to 1.66
Aspirin	Voelker 2016 USA	Adult Outpatient URTI	1000 mg Aspirin p.o. single dose (n = 71)	Placebo (n = 36)			VAS^h Summed Pain Intensity Differences (0‐100mm, 0–2hr) mean difference (95% CI)			GI upset RR (95% CI)
‐34.6 ‐46.77 to −22.43
First Pain Relief in minutes median (95% CI)
33.3 (28.9, 41.7)	90.8 (45.8, NA)	0.507 0.11 to 2.39
Pain score Relieved by first dose Mean difference (95% CI)
RR= 1.73 1.26 to 2.38

Kor 2016 Mayo Clinic USA	Adult Inpatient ARDS	Aspirin 325mg I.V. day 1, followed by 81mg of I.V. daily up to day 7 (n = 195)	placebo (n = 195)				ARDS development within 7‐days RR (95% CI)	ICU length of stay Median (1st to 3rd quartile)	GI upset RR (95% CI)
3.2 (1.8 to 6.0)	2.4 (1.6 to 5.2)
RR = 1.18 0.64 to 2.18	ICU length of stay Mean difference (95% CI)
0.20 ‐1.19 to 1.59	1 0.06 to 15.87
Ventilator‐free to day 28 (ventilated patients) Median (Q1‐Q3)	Hospital length of stay Median (1st to 3rd quartile)
5.0 (3.0 to 10.0)	6.0 (4.0 to 10.0)
23.0 (17.0 to 26.0)	23.0 (9.0 to 26.0)	Hospital length of stay Mean difference (95% CI)	GI bleeding RR (95% CI)
0.200 ‐1.81 to 2.21
Ventilator‐free to day 28 (ventilated patients) mean difference (95% CI)	Mortality 28‐days RR (95% CI)
1 0.49 to 2.04	1.5 0.25 to 8.88
‐0.30 ‐1.13 to 1.73	Mortality 1‐year RR (95% CI)
1.02 0.71 to 1.47

Eccles 2013 U.K.	Adult Outpatient Sore throat	Aspirin 1000mg p.o. daily for 3 days (n = 239)	Placebo (n = 121)			Total pain relief (0‐3 score) 0‐4hr Mean difference (95% CI)			GI upset RR (95% CI)

−0.1 −0.11 to −0.09	1.82 0.69 to 4.79

Eccles 2003 U.K./Sweden	Adult Outpatient URTI	Aspirin 800mg p.o. daily for 3 days (n = 139)	Placebo (n = 133)			Sum of pain intensity difference (0–3 score) 0–2hr Mean difference (95% CI)			GI upset RR (95% CI)
−1.4 −2.01 to −0.79	1.59 0.39 to 6.54
Broggini 1986 Italy	Adult Outpatient Influenza	Aspirin 500mg p.o. BD for 4 days (n = 15)	Flurbiprofen 100mg p.o. BD for 4 days (n = 15)	6 h fever temperature Mean difference (95% CI)	4th day Cough relief RR (95% CI)	4th day Pharyngeal pain relief RR (95% CI)			GI upset RR (95% CI)
−0.10 −0.32 to 0.12	3.9 0.47 to 32.09	1.15 0.55 to 2.39	1.00 0.16 to 6.20
Loose 2011 U.S.A.	Adult outpatient URTI	Aspirin 1000mg + 60mg Pseudoephedrine single dose p.o. (n = 161)	Placebo (n = 162)						GI upset RR (95% CI)
1.00 0.25 to 3.95
Bachert 2005 Russia/ Ukraine	Adult Outpatient URTI	Aspirin 1000mg p.o. single dose (n = 78)	Placebo (n = 78)	Feverish discomfort 0––6 h (0–10 score) Mean difference (95% CI)		Sore throat (0–10 score) Mean difference (95% CI)			GI upset RR (95% CI)
−2.9 −3.00 to −2.80
Maximum temperature reduction in 6hr Mean difference (95% CI)	−0.49 −0.62 to −0.36	3.33 0.95 to 11.65
−1.04 −1.08 to −1.00
	Barberi Italy 1993	Pediatric Inpatient/ Outpatient URTI/LRTI	Aspirin 360mg p.o. BD for 5 days (n = 35)	Nimesulide 50mg p.o. BD for 5 days (n = 35)		Day 2 Cough (0–3 score) Mean difference (95% CI)	Day 2 Pharyngeal hyperemia (0–3 score) Mean difference (95% CI)			GI upset RR (95% CI)
−0.18 (−0.25 to −0.11)
Day 3 Cough (0–3 score) Mean difference (95% CI)	0 −0.14 to 0.14
−0.14 −0.22 to −0.06
Day 2 Dyspnea (0–3 score) Mean difference (95% CI)	Day 3 Pharyngeal hyperemia (0–3 score) Mean difference (95% CI)	2.67 0.77 to 9.23
−0.22 −0.37 to −0.07
Day 3 Dyspnea (0–3 score) Mean difference (95% CI)	−0.08 −0.21 to 0.05
−0.34 −0.49 to −0.19
	Kondoth 1984 India	Pediatric Inpatient/ Outpatient Fever	Aspirin 15 mg/kg daily for 2 days (n = 14)	Ibuprofen 7mg/kg daily for 2 days (n = 14)	6 h fever reduction (˚C) in patients with URTI Mean difference (95% CI)					Total AE RR (95% CI)
−0.33 −0.13 to −0.53
4 h fever reduction (˚C) in patients with URTI Mean difference (95% CI)	1 0.02 to 47.19
−0.57 −0.42 to −0.72
Other NSAIDs	De Looze, F. 2018 Australia	Adult Outpatient URTI	Flurbiprofen 8.75 mg spray (three puffs), not allowed to redose for 6 hr, then redose every 3–6 h up to 5 doses/day for 3 days, as required (n = 249)	Placebo spray (n = 256)			Number of patients with at least moderate relief at 75mins RR (95% CI)
1.96 1.45 to 2.64
6 h TOTPAR sore throat pain relief
−0.77 −0.80 to −0.74
Azuma, A. 2010 Japan	Adult Outpatient URTI	Zaltoprofen 160 mg p.o. single dose (n = 56)	Placebo (n = 57)	6 h body temperature Mean difference (95% CI)		Visual Analogue Scale (0–100 score) sore throat first dose Mean difference (95% CI)
−0.4 −0.45 to −0.35	−7.80 −9.20 to −6.40
Goto, M. 2007 Japan	Adult Outpatient URTI	Loxoprofen sodium 60 mg p.o. BD for 7 days (n = 84)	Placebo (n = 90)	Fever duration days Mean difference (95% CI)	Cough duration days Mean difference (95% CI)	Sore throat Duration (days) Mean difference (95% CI)		Illness duration days Mean difference (95% CI)	Number of patients with all adverse events (not confined to GI) RR (95% CI)
0.04 −0.71 to 0.79
maximum body temperature Mean difference (95% CI)	−0.62 −1.84 to 0.60	−0.46 −1.42 to 0.50	−0.55 −1.54 to 0.44	8.57 1.10 to 67.09
0 −0.23 to 0.23
Weckx, L. 2002 Latin America	Adult Outpatient Pharyngitis	Celecoxib 200mg p.o. BD for 5 days (n = 117)	Diclofenac 75mg p.o. BD for 5 days (n = 101)						GI upset RR (95% CI)
0.3837 0.1218 to 1.2085

Passali, D 2001 Italy	Adult Outpatient Pharyngitis	Mouthwash Ketoprofen lysine salt 160mg gargled twice daily (until pain remission or up to 7 days) (n = 119)	Mouthwash Benzydamine hydrochloride 22.5mg gargled twice daily (until pain remission or up to 7 days) (n = 120)			No. of patients with Pain reduced to mild/ absent RR (95% CI)			Dry mouth RR (95% CI)
1.04 0.98 to 1.09
No. of patients who completely recovered RR (95% CI)	0.46 0.27 to 0.79
1.12 0.95 to 1.32
Ebel 1985 U.S.A.	Adult Inpatient URTI	Sulindac 200mg BD for 7 days (n = 156)	Placebo (n = 156)	No. with >1˚C fever reduction day 1 RR (95% CI)					GI upset RR (95% CI)
1.68 1.21 to 2.35
No. with >1˚C fever reduction day 2 RR (95% CI)
1.21 0.98 to 1.48	2 1.10 to 3.65
Day7 no. without fever RR (95% CI)
1.26 1.11 to 1.43

Choi, S.J. 2018 South Korea	Pediatric Inpatient URTI	Propacetamol IV/inf. <10 kg : 15 mg/kg >10 kg : 30 mg/kg Single dose (n = 125)	Dexibuprofen 6 mg/kg IV/inf. Stat + Placebo (n = 138)	6 h No. of Normalized Fever RR (95% CI)					GI upset RR (95% CI)
1.25 0.75 to 2.07
4 h Fever Mean difference (95% CI)
0.19 −0.03 to 0.41	0.46 0.17 to 1.27
6 h Fever Mean difference (95% CI)
0.01 −0.16 to 0.18

NSAID

Study

Participants age & setting

Intervention (number of participants)

Comparison (number of participants)

Outcomes

Fever

Cough

Sore Throat

ARDS

Length of Stay / Mortality

Gastrointestinal Adverse Events

Ibuprofen

Llor, C.

2013

Spain

Adult

Inpatient

ARTI

Ibuprofen 600 mg TDS

For 10 days

(n = 136)

Placebo

(n = 143)

Number of days with cough

Mean difference (95% CI^d)

GI upset

RR (95% CI)

1.5 to 2.5

1.84

0.55 to 6.15

Bernard, G. R.

1997

North America

Adult

Inpatient

Sepsis Criteria

Ibuprofen IV/inf./ 10 mg/kg QID (maximal dose: 800 mg daily) for 2 days

(n = 224)

Placebo

(n = 231)

4 h Fever

Mean difference (95% CI)

24 h Minute‐Ventilation (L/min)

Mean difference (95% CI)

30‐day Mortality

RR (95% CI)

GI Bleeding

RR (95% CI)

−0.80

−0.78 to −0.82

0.92

0.85 to 0.99

0.88

0.70 to 1.11

0.58

0.26 to 1.29

Bouroubi, A.

2017

Europe

Adult

Outpatient

Sore Throat

Ibuprofen 25mg lozenge p.o. up to 6 doses daily

for 4 days

(n = 194)

Placebo lozenges p.o.

for 4 days

(n = 191)

4th day pain Relieved

RR (95% CI)

GI upset

RR (95% CI)

1.51

1.06 to 2.15

2.95

0.60 to 14.45

Little, P.

2013

United Kingdom

Adult & Pediatrics

Outpatient

ARTI

Ibuprofen

200–400 mg p.o. QID

for 3 days

(n = 150)

Paracetamol 15 mg/kg p.o. QID for 3 days

(n = 152)

GI upset RR (95% CI)

0.83

0.63 to 1.10

Winther, B.

2001

Denmark

Adult

Outpatient

URTI

Ibuprofen 400 mg p.o. TDS for 3 days

(n = 38)

Placebo

(n = 42)

Chilliness improvement 3‐day (0–9 score)

Mean difference (95% CI)

Cough improvement 3‐day (0–9 score)

Mean difference (95% CI)

Sore Throat improvement 3‐day (0–9 score)

Mean difference (95% CI)

0.63

0.75 to 0.51

0.83

1.05 to 0.61

0.31

0.48 to 0.14

Gwaltney, J. M., Jr.

2002

USA

Adult

Outpatient

Rhinovirus

Inoculation

Intranasal placebo + oral chlorpheniramine (12 mg extended release) and

Tab. Ibuprofen 400 mg BD for 5 days

(n = 61)

Intranasal and oral placebos

(n = 30)

3rd day Cough (0–4 score)

Mean difference (95% CI)

3rd day Sore throat (0–4 score)

Mean difference (95% CI)

−0.12

−0.09 to −0.15

−0.24

−0.20 to −0.28

Sperber, S. J.

1989

USA

Adult

Outpatient

Rhinovirus

Inoculation

Pseudoephedrine HC1 60 mg + Ibuprofen 200 mg p.o. for 5 days

(n = 23)

Pseudoephedrine HC1 60 mg + placebo p.o.

for 5 days

(n = 23)

Sore Throat (0–18 score)

Mean difference (95% CI)

GI upset

RR (95% CI)

−1

−3.10 to 1.10

0.33

0.01 to 7.78

Kim, C‐K.

2013

South Korea

Pediatric

Outpatient

URTI

Dexibuprofen 3.5 or 7 mg/kg p.o. single dose

(n = 75)

Ibuprofen 5 or 10 mg/kg p.o. single dose

(n = 76)

4 h Fever

Mean difference (95% CI)

GI upset

RR (95% CI)

0.26

−0.0232 to 0.5432

0.98

0.70 to 1.39

Hay AD.

2008

United Kingdom

Pediatric

Outpatient

Fever

Ibuprofen 10 mg/kg p.o. q6–8hr

for 2 days

(n = 52)

Paracetamol 15 mg/kg p.o. q4–6hr

for 2 days

(n = 52)

Time until first fever clearance (minutes)

Mean difference (95% CI)

2nd day Recovered child

RR (95% CI)

GI upset

RR (95% CI)

28.8

7.68 to 49.92

0.97

0.52 to 1.80

2nd day temperature Mean difference (95% CI)

5th day Recovered child

RR (95% CI)

0.75

0.39 to 1.43

−0.34 to 0.34

0.83

0.49 to 1.38

Yoon, J. S.

2008

South Korea

Pediatric

Outpatient

URTI

Ibuprofen 10 mg/kg p.o. single dose

(n = 85)

Dexibuprofen 5 mg/kg p.o. single dose

(n = 86)

6 h Fever Reduction

Mean difference (95% CI)

GI upset

RR (95% CI)

−0.1

‐0.39 to 0.19

6 h Fever reduced to normal

RR (95% CI)

1.01

0.37 to 2.76

1.40

0.96 to 2.03

Ulukol, B.

1999

Turkey

Pediatric

Outpatient

URTI

Ibuprofen (suspension) 10 mg/kg p.o. TDS + Anti‐Biotics

for 5 days

(n = 30)

Paracetamol

(suspension) 10 mg/kg p.o. TDS + Anti‐Biotics

(n = 30)

Fever improved 2nd day

RR (95% CI)

Cough improved 5th day

RR (95% CI)

0.60

0.33 to 1.12

0.79

0.60 to 1.06

Bertin, L.

1991

France

Pediatric

Outpatient

Sore Throat

Ibuprofen 10 mg/kg p.o. TDS

+ penicillin for 7 days

(n = 77)

Placebo

+ penicillin for 7 days

(n = 76)

2nd day pain relief

RR (95% CI)

GI upset

RR (95% CI)

1.68

1.27 to 2.23

0.99

0.30 to 3.27

Naproxen

Hung

2017

Hong Kong

(H3N2) influenza inpatient

Adult

clarithromycin 500 mg, naproxen 200mg, and oseltamivir 75 mg BD for 2 days, followed by 3 days of

oseltamivir 75 mg BD

(n = 107)

oseltamivir

75 mg BD for 5 days

(n = 110)

Respiratory support during hospitalization

RR (95% CI)

Days of Acute care hospitalization median (1st to 3rd quartile)

0.53

0.33 to 0.83

2 (1–3)

3 (2–4)

HDU admission required during hospitalization

RR (95% CI)

30‐day mortality

RR (95% CI)

0.51

0.31 to 0.86

0.11

0.01 to 0.89

ICU^h admission required during hospitalization

RR (95% CI)

90‐day mortality

RR (95% CI)

0.29

0.06 to 1.38

0.19

0.04 to 0.82

Sperber, S. J.

1992

USA

Outpatient

Adults

Viral inoculation with RSV

Naproxen 400 mg or 500 mg p.o. stat followed by

200 mg or 500 mg TDS for 5 days

(n = 39)

Placebo

(n = 40)

5th day Chilliness (0–4 score)

Mean difference (95% CI)

5th day Cough (0–4 score)

Mean difference (95% CI)

5th day Sore throat (0–4 score)

Mean difference (95% CI)

GI Upset

RR (95% CI)

0.40

−0.11 to 0.91

Fever developed (Temp. >37.5)

RR (95% CI)

0.8

−0.17 to 1.80

0.5

−0.93 to 1.90

0.53

0.05 to 5.57

0.14

0.03 to 0.59

Gwaltney, J. M., Jr.

1992

USA

Outpatient

Adults

Viral inoculation with RSV

‐Naproxen 500 mg stat and then 250 mg TDS

‐Ipratropium 80 mcg (2 puffs/ nostril) TDS

‐IFN‐a2b 3 million units (0.1 mL/nostril) TDS

for 4 days

(n = 16)

Placebo

(n = 8)

GI Upset

RR (95% CI)

1.59

0.07 to 35.15

Salmon Rodriguez, L. E.

1993

Mexico

(Probably inpatient)

Pediatrics

Sore Throat

Naproxen TDS p.o. for 8 days

Dosing:

(25 mg per ml):

−2.5 ml for 1 to 3 years.

−5 ml for 4 to7 years.

−7.5 ml for 8 to 10 years.

(n = 50)

Nimesulide BD p.o. for 8 days

Dosing:

(l0 mg per ml):

‐ 2.5 ml for 1 to 3 years.

‐ 5 ml for 4to 7 years.

‐ 7.5 ml for 8 to 10 years.

‐ 10 ml for more than 10 years.

(n = 49)

GI Upset

RR (95% CI)

2.73

0.95 to 7.89

Diclofenac

Grebe

2003

Germany

Adult

Outpatient

Influenza‐like symptoms

Diclofenac 25mg p.o. daily

For 3 days

(n = 121)

Placebo

(n = 115)

6 h Fever under 37.8˚C

RR (95% CI)

GI Upset

RR (95% CI)

2.73

1.27 to 5.86

0.48

0.043 to 5.17

Weckx

2002

Brazil/

Columbia/

Mexico

Adult

Outpatient

Influenza‐like symptoms

Diclofenac 75 mg p.o.

BD for 5 days

(n = 101)

celecoxib 200 mg p.o. BD for 5 days

(n = 107)

3rd day Visual Analogue Scale (100 points)

Mean difference (95% CI)

GI Upset

RR (95% CI)

2.14

1.56 to 2.72

2.14

0.68 to 6.76

Bettini

1986

Italy

Adult

Outpatient

Influenza‐like symptoms

Diclofenac 25 mg p.o. BD

For 2 days

(n = 60)

500 mg Aspirin p.o. TDS for 2 days

(n = 60)

6 h Fever

Mean Difference (95% CI)

2nd day sore throat moderate symptom reduction

RR (95% CI)

GI Upset

RR (95% CI)

0.9

0.5 to 1.3

0.99

0.77 to 1.28

0.2

0.02 to 1.66

Aspirin

Voelker

2016

USA

Adult

Outpatient

URTI

1000 mg Aspirin p.o. single dose

(n = 71)

Placebo

(n = 36)

VAS^h Summed Pain Intensity Differences (0‐100mm, 0–2hr) mean difference (95% CI)

GI upset

RR (95% CI)

‐34.6

‐46.77 to −22.43

First Pain Relief in minutes median (95% CI)

33.3 (28.9, 41.7)

90.8 (45.8, NA)

0.507

0.11 to 2.39

Pain score Relieved by first dose

Mean difference (95% CI)

RR= 1.73

1.26 to 2.38

Kor

2016

Mayo Clinic

USA

Adult

Inpatient

ARDS

Aspirin 325mg

I.V. day 1, followed by 81mg of I.V. daily

up to day 7

(n = 195)

placebo

(n = 195)

ARDS development within 7‐days

RR (95% CI)

ICU length of stay Median (1st to 3rd quartile)

GI upset

RR (95% CI)

3.2 (1.8 to 6.0)

2.4 (1.6 to 5.2)

RR = 1.18

0.64 to 2.18

ICU length of stay Mean difference (95% CI)

0.20

‐1.19 to 1.59

0.06 to 15.87

Ventilator‐free to day 28 (ventilated patients)

Median (Q1‐Q3)

Hospital length of stay Median (1st to 3rd quartile)

5.0 (3.0 to 10.0)

6.0 (4.0 to 10.0)

23.0 (17.0 to 26.0)

23.0 (9.0 to 26.0)

Hospital length of stay

Mean difference (95% CI)

GI bleeding

RR (95% CI)

0.200

‐1.81 to 2.21

Ventilator‐free to day 28 (ventilated patients)

mean difference (95% CI)

Mortality 28‐days

RR (95% CI)

0.49 to 2.04

1.5

0.25 to 8.88

‐0.30

‐1.13 to 1.73

Mortality 1‐year

RR (95% CI)

1.02

0.71 to 1.47

Eccles

2013

U.K.

Adult

Outpatient

Sore throat

Aspirin 1000mg p.o. daily for 3 days

(n = 239)

Placebo

(n = 121)

Total pain relief (0‐3 score) 0‐4hr

Mean difference (95% CI)

GI upset

RR (95% CI)

−0.1

−0.11 to −0.09

1.82

0.69 to 4.79

Eccles

2003

U.K./Sweden

Adult

Outpatient

URTI

Aspirin

800mg p.o. daily for 3 days

(n = 139)

Placebo

(n = 133)

Sum of pain intensity difference (0–3 score)

0–2hr

Mean difference (95% CI)

GI upset

RR (95% CI)

−1.4

−2.01 to −0.79

1.59

0.39 to 6.54

Broggini

1986

Italy

Adult Outpatient

Influenza

Aspirin 500mg p.o. BD for 4 days

(n = 15)

Flurbiprofen 100mg p.o. BD for 4 days

(n = 15)

6 h fever temperature Mean difference (95% CI)

4th day Cough relief

RR (95% CI)

4th day Pharyngeal pain relief

RR (95% CI)

GI upset

RR (95% CI)

−0.10

−0.32 to 0.12

3.9

0.47 to 32.09

1.15

0.55 to 2.39

1.00

0.16 to 6.20

Loose

2011

U.S.A.

Adult outpatient URTI

Aspirin 1000mg + 60mg Pseudoephedrine single dose p.o.

(n = 161)

Placebo

(n = 162)

GI upset

RR (95% CI)

1.00

0.25 to 3.95

Bachert

2005

Russia/

Ukraine

Adult Outpatient URTI

Aspirin

1000mg p.o. single dose

(n = 78)

Placebo

(n = 78)

Feverish discomfort 0––6 h (0–10 score) Mean difference (95% CI)

Sore throat (0–10 score) Mean difference (95% CI)

GI upset

RR (95% CI)

−2.9

−3.00 to −2.80

Maximum temperature reduction in 6hr

Mean difference (95% CI)

−0.49

−0.62 to −0.36

3.33

0.95 to 11.65

−1.04

−1.08 to −1.00

Barberi

Italy

1993

Pediatric

Inpatient/

Outpatient

URTI/LRTI

Aspirin

360mg p.o. BD for 5 days

(n = 35)

Nimesulide

50mg p.o. BD for 5 days

(n = 35)

Day 2 Cough (0–3 score) Mean difference (95% CI)

Day 2 Pharyngeal hyperemia (0–3 score) Mean difference (95% CI)

GI upset

RR (95% CI)

−0.18

(−0.25 to −0.11)

Day 3 Cough (0–3 score) Mean difference (95% CI)

−0.14 to 0.14

−0.14

−0.22 to −0.06

Day 2 Dyspnea (0–3 score) Mean difference (95% CI)

Day 3 Pharyngeal hyperemia (0–3 score) Mean difference (95% CI)

2.67

0.77 to 9.23

−0.22

−0.37 to −0.07

Day 3

Dyspnea (0–3 score) Mean difference (95% CI)

−0.08

−0.21 to 0.05

−0.34

−0.49 to −0.19

Kondoth

1984

India

Pediatric

Inpatient/

Outpatient

Fever

Aspirin 15 mg/kg daily for 2 days

(n = 14)

Ibuprofen 7mg/kg daily for 2 days

(n = 14)

6 h fever reduction (˚C) in patients with URTI Mean difference (95% CI)

Total AE

RR (95% CI)

−0.33

−0.13 to −0.53

4 h fever reduction (˚C) in patients with URTI Mean difference (95% CI)

0.02 to 47.19

−0.57

−0.42 to −0.72

Other NSAIDs

De Looze, F.

2018

Australia

Adult

Outpatient

URTI

Flurbiprofen 8.75 mg spray

(three puffs), not allowed to redose for 6 hr, then redose every 3–6 h up to 5 doses/day for 3 days, as required

(n = 249)

Placebo spray

(n = 256)

Number of patients with at least moderate relief at 75mins

RR (95% CI)

1.96

1.45 to 2.64

6 h TOTPAR sore throat pain relief

−0.77

−0.80 to −0.74

Azuma, A.

2010

Japan

Adult

Outpatient

URTI

Zaltoprofen 160 mg p.o.

single dose

(n = 56)

Placebo

(n = 57)

6 h body temperature

Mean difference (95% CI)

Visual Analogue Scale (0–100 score) sore throat first dose

Mean difference (95% CI)

−0.4

−0.45 to −0.35

−7.80

−9.20 to −6.40

Goto, M.

2007

Japan

Adult

Outpatient

URTI

Loxoprofen

sodium 60 mg p.o. BD for 7 days

(n = 84)

Placebo

(n = 90)

Fever duration days

Mean difference (95% CI)

Cough duration days Mean difference (95% CI)

Sore throat

Duration (days)

Mean difference (95% CI)

Illness duration days

Mean difference (95% CI)

Number of patients with all adverse events (not confined to GI)

RR (95% CI)

0.04

−0.71 to 0.79

maximum body temperature

Mean difference (95% CI)

−0.62

−1.84 to 0.60

−0.46

−1.42 to 0.50

−0.55

−1.54 to 0.44

8.57

1.10 to 67.09

−0.23 to 0.23

Weckx, L.

2002

Latin America

Adult

Outpatient

Pharyngitis

Celecoxib 200mg p.o. BD for 5 days

(n = 117)

Diclofenac 75mg p.o. BD for 5 days

(n = 101)

GI upset

RR (95% CI)

0.3837

0.1218 to 1.2085

Passali, D

2001

Italy

Adult

Outpatient

Pharyngitis

Mouthwash

Ketoprofen lysine salt

160mg

gargled twice daily (until pain remission or up to 7 days)

(n = 119)

Mouthwash

Benzydamine hydrochloride

22.5mg

gargled twice daily (until pain remission or up to 7 days)

(n = 120)

No. of patients with Pain reduced to mild/ absent

RR (95% CI)

Dry mouth

RR (95% CI)

1.04

0.98 to 1.09

No. of patients who completely recovered

RR (95% CI)

0.46

0.27 to 0.79

1.12

0.95 to 1.32

Ebel

1985

U.S.A.

Adult

Inpatient

URTI

Sulindac 200mg BD for 7 days

(n = 156)

Placebo

(n = 156)

No. with >1˚C fever reduction day 1

RR (95% CI)

GI upset

RR (95% CI)

1.68

1.21 to 2.35

No. with >1˚C fever reduction day 2

RR (95% CI)

1.21

0.98 to 1.48

1.10 to 3.65

Day7 no. without fever

RR (95% CI)

1.26

1.11 to 1.43

Choi, S.J.

2018

South Korea

Pediatric

Inpatient

URTI

Propacetamol IV/inf.

<10 kg : 15 mg/kg

>10 kg :

30 mg/kg

Single dose

(n = 125)

Dexibuprofen 6 mg/kg IV/inf. Stat + Placebo

(n = 138)

6 h No. of Normalized Fever

RR (95% CI)

GI upset

RR (95% CI)

1.25

0.75 to 2.07

4 h Fever

Mean difference (95% CI)

0.19

−0.03 to 0.41

0.46

0.17 to 1.27

6 h Fever

Mean difference (95% CI)

0.01

−0.16 to 0.18

Interventions: BD, two doses daily; TDS, three doses per day; QID, four doses per day; p.o., oral intake; I.V., intra venous; Inf., infusion; Stat., immediately.

Abbreviations: ARDS: Acute Respiratory Distress Syndrome; ARTI, acute respiratory tract infection; CI, Confidence Interval; GI, Gastrointestinal; ICU, intensive care unitRR, Relative Risk; RSV, Respiratory Syncytial Virus; URTI, upper respiratory tract infection; VAS, visual analogue scale.