Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Ecevit, 2015

Type of study:

RCT

Setting and country:

Single-centre, Turkey

Funding and conflicts of interest:

The authors have no funding, financial relationships, or conflicts

of interest to disclose.

Inclusion criteria:

Nasal polyposis; 18-65 years old; Endoscopic stage II or III nasal polyposis; no response to 6 weeks of fluticasone nasal drops.

Exclusion criteria:

Hypertension, type I or II diabetes mellitus, signs of systemic infection, pregnancy/lactation, any type of tuberculosis infection, peptic ulcer, viral infection, myasthenia gravis, stage I nasal polyposis, aspirin intolerance, previous major head trauma.

N total at baseline:

Intervention: 10

Control: 12

Important prognostic factors²:

Age, mean ± SD:

I: 45.6±11.5

C: 19.2±3.1

Sex:

I: 90% M

C: 67% M

Groups were comparable at baseline.

Oral  prednisolone, 60 mg for 7 days, followed by 10 mg every other day for 10 days.

N=10

Oral placebo.

N=12

Length of follow-up:

17 days

Loss-to-follow-up:

None.

Incomplete outcome data:

Not specified.

Values are mean ± SD after treatment

Polyp score (data taken from EPOS position paper):

OCS: 2.2±0.42 (n=10)

Placebo: 2.8±0.49 (n=12)

Mean difference -1.26 [95% CI -2.19, -0.32]

Smell (VAS, higher is worse)

OCS: 5.5±3.6

Placebo: 8.5±2.2

Adverse effects were not observed in either group.

Authors’ conclusions:

Preoperative administration of systemic corticosteroids

improves perioperative visibility by reducing blood

loss and results in the shortening of the operation time. We advise utilization of preoperative corticosteroid for the safety of patients being treated for nasal polyposis. The optimal dose and duration of medication to use in these cases require additional study.

Kirtsreesakul, 2012

Type of study:

RCT

Setting and country:

Single-centre, Thailand

Funding and conflicts of interest:

Funded by the Faculty of Medicine, Prince of Songkla University.

The authors have no conflicts of interest to declare pertaining to this article

Inclusion criteria:

Patients with benign bilateral nasal polyps diagnosed clinically and confirmed by nasal endoscopy were included in the study.

Exclusion criteria:

Patients with symptoms or physical signs suggestive of renal disease, hepatic disease, diabetes mellitus, cataract, glaucoma, cardiovascular disease, unstable asthma, cystic fibrosis, mucociliary disorders, immunocompromise, severe septal deviation, or acute infection within the previous 2 months; patients who had used nasal, inhaled, or systemic steroids within 2 months, an antihistamine within 2–7 days, and/or a decongestant within 2 days or had had previous sinonasal surgery.

N total at baseline:

Intervention: 69

Control: 48

Important prognostic factors²:

Age, mean (range):

I: 45.3 (18-65)

C: 46.4 (18-65)

Sex:

I: 64% male

C: 62% male

Mean duration of symptoms (yr):

I: 7.9

C: 7.7

Total nasal polyp score, mean ± SD:

I: 3.37 ± 1.37

C: 3.13 ± 1.09

Groups were comparable at baseline.

Oral Behandel patiënten met chronische rhinosinusitis in het algemeen zo weinig mogelijk met systemische corticosteroïden.

Overweeg bij patiënten met prednisolone, 50 mg  daily for 14 days

Placebo for 14 days

followed in both groups by administration of mometasone furoate nasal spray (MFNS) at 200 µg twice daily for 10 weeks.

Length of follow-up:

12 weeks

Loss-to-follow-up:

Intervention: 2/69 (3%)

Logistical reasons

Control: 1/48 (2%)

Logistical reasons

Incomplete outcome data:

None

Outcome measures and effect size (include 95%CI and p-value if available):

Total symptom score (data from EPOS position paper) mean±SD

OCS: 7.73±14.16 (n=67)

C: 9.75±13.83 (n=47)

Mean difference -2.02 [95% CI -7.23, 3.19]

Polyp score (data from EPOS position paper) mean±SD

At 2 weeks

OCS: 1.92±1.37

C: 3.13±1.09

Mean difference -1.21 [95% CI -1.66, -0.76]

At 12 weeks

OCS: 1.79±1.37

C: 2.22±1.09

Mean difference -0.43 [95% CI -0.88, 0.02]

Adverse effects

(specified per event, not per person)

OCS vs C:

Gastrointestinal disturbance: 11 vs 1

Dyspepsia: 5 vs 1

Throat irritation: 4 vs 3

Headache: 3 vs 3

Nasal irritation: 2 vs 2

Increased appetite: 1 vs 0

Fatigue: 1 vs 0

Acne: 1 vs 0

Insomnia: 1 vs 0

Authors’ conclusions:

Combined oral and nasal steroid therapy was more effective over 12 weeks than nasal steroid therapy alone in improving hyposmia,

polyps size, and nasal airflow in nasal polyposis.

Vaidyanathan, 2011

Type of study:

RCT

Setting and country:

Single-centre, Scotland

Funding and conflicts of interest: Chief Scientist Office, Scotland; National Health Service Tayside Small Grants Scheme; and an Anonymous Trust grant from University of Dundee.

Inclusion criteria:

Nonsmoking adults who had CRS with

nasal polyposis, with or without asthma, from a single-centre

specialty clinic in Tayside, Scotland, to which patients were referred for assessment by their primary care physicians.

Inclusion criteria were the presence on nasoendoscopy of bilateral moderate-sized to large nasal polyps (grade >1) according to the Lildholdt scale and at least 2 of anterior or posterior nasal discharge, nasal obstruction, or decreased sense of smell for more than 12 weeks.

Exclusion criteria:

Treatment with an oral corticosteroid in the past 3 months, sinus surgery in the past year, recent upper respiratory tract infection, mechanical nasal airway obstruction of more than 50% due to septal deviation, or pregnancy or lactation.

N total at baseline:

Intervention: 30

Control: 30

Important prognostic factors²:

Age mean (range):

I: 49 (24–70)

C: 52 (17–78)

Sex:

I: 47% M

C: 67% M

Duration of CRS, mean±SD (years)

I: 11±11

C: 17±15

Groups were comparable at baseline.

Oral prednisolone 25mg/day for 2 weeks

N=29

Placebo tablets for 2 weeks.

N=29

followed in both groups by

fluticasone propionate nasal drops 400 µg twice daily, for 8 weeks and then fluticasone propionate nasal

spray, 200 µg twice daily, for a further 18 weeks.

Length of follow-up:

28 weeks

Loss-to-follow-up:

Intervention: 3/30 (10%)

1 withdrew for personal reasons, 2 did not receive follow-up medication (nasal spray)

Control: 6/30 (20%)

1 withdrew for personal reasons, 1 was lost to follow-up, 2 discontinued placebo intervention due to nausea or asthma exacerbation, 2 did not receive follow-up medication (nasal spray).

Incomplete outcome data:

I: 3% of the data for polyp grading were missing at 2 weeks, 7% at 10 weeks, and 4% at 28 weeks.

C: 7% of the data were missing at 2 weeks, 7% at 10 weeks, and 4% at 28 weeks.

Total symptom score

mean (95% CI)

At 2 weeks

I: 1.03 (0.40 to 1.67)

C: 3.22 (1.86 to 4.57)

Predicted Mean difference 0.15 (0.02 to 0.40)

P=0.001

At 10 weeks

I: 1.14 (0.69 to 1.59)

C: 1.30 (0.69 to 1.91)

Predicted Mean difference 1.86 (0.85 to 3.98)

P=0.07

At 28 weeks

I: 1.00 (0.58 to 1.41)

C: 1.54 (0.95 to 2.14)

Predicted Mean difference 0.80 (0.26 to 2.15)

P=0.81

Polyp score

mean (95% CI)

At 2 weeks

I: 2.6 (2.1 to 3.1)

C: 4.7 (4.4 to 5.0)

Predicted Mean difference -1.8 (–2.4 to –1.2)

P<0.001

At 10 weeks

I: 2.2 (1.6 to 2.8)

C: 3.2 (2.8 to 3.5)

Predicted Mean difference

-1.1 (–1.7 to –0.4)

P=0.110

At 28 weeks, mean (95% CI)

I: 2.8 (2.2 to 3.4)

C: 3.3 (2.8 to 3.7)

Predicted Mean difference

-0.8 (–1.8 to 0.2)

P=0.11

Hyposmia VAS (0–100 mm, lower score equals better smell)

At 2 weeks

I: 27.52 (18.37 to 38.53)

C: 54.55 (41.29 to 69.64)

Predicted Mean difference -28.33

(–42.71 to –13.96)

P=0.002

At 10 weeks

I: 27.24 (17.41 to 39.25)

C: 38.12 (26.31 to 52.10)

Predicted Mean difference -16.06

(–30.99 to –1.13)

P=0.03

At 28 weeks

I: 29.27 (19.84 to 40.53)

C: 41.33 (28.96 to 55.92)

Predicted Mean difference -12.13

(–30.55 to 6.29)

P=0.19

Authors’ conclusions:

Initial oral steroid therapy followed by topical steroid therapy seems to be more effective over 6 months than topical steroid therapy alone in decreasing polyp size and improving olfaction in patients referred for specialty care of CRS with at least moderate nasal polyposis.

Van Zele, 2010

Type of study:

RCT

Setting and country:

Multicentre, Belgium, Germany, Australia, the Netherlands

Funding and conflicts of interest:

Supported by a grant from the Flemish Scientific Research Board, FWO Nr. A12/5-HBKH 3 (holder of a Fundamenteel Klinisch Mandaat), by a postdoctoral grant from the Research Foundation Flanders (FWO), and by postdoctoral mandate from the Research Foundation Flanders (FWO). Disclosure of potential conflict of interest: P. J. Wormald has received royalties from Medtronic ENT, is a consultant for NeilMed, and has received research support from the Garnett Passe and RodneyWilliams Foundation.W. Fokkens has received research support from GlaxoSmithKline and Stallergenes. A. Beule has received research support from the European Union. The rest of the authors have declared that they have no conflict of interest.

Inclusion criteria:

Patients with recurrent bilateral nasal polyps after surgery or massive bilateral nasal polyps (grade 3 or 4) in good health, and free of diseases that would interfere with the study.

Exclusion criteria:

Women must not be pregnant, breast-feeding, or premenarcheal. Subjects who have required a burst of oral corticosteroids within the 3 months before screening are excluded from the study. Subjects with systemic fungoid infections, known allergic reaction on methylprednisolone or tetracyclines, hypertension, diabetes (type 1 and 2), glaucoma, tuberculosis, herpes infection, or zona ophtalmica are excluded, and children are excluded. For all criteria see supplemental table E2 of the article.

N total at baseline:

Intervention: 14

Control: 19

Important prognostic factors²:

Age, mean (SEM):

I: 48.89 (3.23)

C: 54.67 (3.07)

Sex:

I: 85.7% M

C: 78.9% M

Total polyp score, mean (SEM):

I: 5.86 (0.27)

C: 6.16 (0.29)

Groups were comparable at baseline.

Group 1. Oral methylprednisolone (32 mg/d on days 1-5; 16 mg/d on days 6-10; and 8 mg/d on days 11-20).

Group 2*. oral doxycycline

*group 2 was not considered in this analysis

Oral placebo

Length of follow-up:

12 weeks

Loss-to-follow-up:

Intervention: 0/14

Control:

7/19 (37%)

after week 4.

Reasons for withdrawal included unsatisfactory therapeutic effects, withdrawal of consent, and serious adverse events

Incomplete outcome data:

Not specified

Total symptom score (data from EPOS position paper)

Mean±SD at 12 weeks

I: 7.62±3.89 (n=14)

C: 7.94±3.44 (n=9)

Mean difference -0.32 [95% CI -2.88, 2.24]

Polyp score (data from EPOS position paper)

Mean±SD

At 1 week

I: 3.46±1.01

C: 5.96±1.26

Mean difference -2.50 [95% CI -3.28,

-1.72]

At 12 weeks

I: 5.61±1.01

C: 6.26±1.26

Mean difference -0.65 [95% CI -1.43, 0.13]

Adverse events: 48.5% of the subjects in the study reported at least 1 adverse event. There were no significant differences in the number or type of adverse events between treatment groups or between treatment and placebo groups.

Authors’ conclusions:

This study highlights the need for long-term studies with doxycycline to establish their therapeutic role in the treatment of nasal polyposis and to improve treatment standards. Treatment of nasal polyps with oral corticosteroids is of limited value unless it is associated with surgery or therapy with intranasal corticosteroids.

Hissaria, 2006

Type of study:

RCT

Setting and country:

Single-centre, Australia

Funding and conflicts of interest:

Funding not stated.

P. Wormwald receives royalties

from Medtronic Xomed for instruments designed. The rest of the authors

have declared that they have no conflict of interest.

Inclusion criteria:

Patients aged 18 to 65 years who had symptomatic polyp disease diagnosed on

nasendoscopy.

Exclusion criteria:

Previous use of oral steroids, unstable asthma, recent sinus surgery, acute infection within 1 month of recruitment, polyps caused by cystic fibrosis or mucociliary disorders, diabetes mellitus, cataract, glaucoma, fungal sinusitis, contraindications for MRI scanning, or any other significant comorbid condition that contraindicated the use of systemic corticosteroids.

N total at baseline:

Intervention: 20

Control: 21

Important prognostic factors²:

For example

Age, mean ± SD:

I: 49±13

C: 48±12

Sex:

I: 35% M

C: 60% M

Previous polyp operations

I: 8/20

C: 13/20

Groups were comparable at baseline.

Oral prednisolone, 50 mg daily for 14 days

Oral placebo

Length of follow-up:

2 weeks

Loss-to-follow-up:

Intervention: 0

Control: One subject (5%)

(in the placebo group) withdrew within the first week because of a lack of efficacy

Incomplete outcome data:

Not specified.

Nasendoscopy polyp score at 14 days (%)

I: 52%

C: 93%

Adverse events (specified per event, not per person) Events, I vs C:

Insomnia, 8 vs 2

Mood disturbance, 5 vs 2

Headache, 2 vs 0

Dyspepsia, 3 vs 2

Increased appetite, 2 vs 0

Fatigue, 2 vs 0

Backache, 1 vs 0

Diarrhea/GI disturbance, 2 vs 1

Acne, 1 vs 0

Edema feet, 1 vs 0

Authors’ conclusions:

This trial clearly establishes clinically significant

improvement in the symptoms and pathology of sinonasal polyposis with a short course of systemic corticosteroids.

Study reference

(first author, publication year)

Was the allocation sequence adequately generated? ^a

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?^b

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?^c

Were patients blinded?

Were healthcare providers blinded?

Were data collectors blinded?

Were outcome assessors blinded?

Were data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?^d

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?^e

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?^f

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/necessary, per outcome measure^g

LOW

Some concerns

HIGH

Ecevit, 2015

Probably yes;

Reason: The hospital pharmacy department performed the drug/placebo randomization, but the randomization method was not specified.

Definitely yes;

Reason: The hospital pharmacy department performed the drug/placebo randomization, and the identity of the contents in the boxes was not disclosed to any clinicians interacting with patients throughout the study.

Definitely yes;

Reason: The hospital pharmacy department performed the drug/placebo randomization, and the identity of the contents in the boxes was not disclosed to any clinicians interacting with patients throughout the study.

Definitely yes;

Reason: no loss to follow-up.

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

LOW

Kirtsreesakul, 2012

Probably yes;

Reason: assumed but not specified.

Probably yes;

Reason: assumed but not specified.

Definitely yes;

Patients and study personnel were not informed of the treatment modality of the patients until all assessments were completed.

Definitely yes;

Loss to follow-up was limited and similar between the groups.

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

LOW

Vaidyanathan, 2011

Definitely yes;

An independent, off-site clinical trials pharmacist used a computer-generated random allocation sequence to randomize the trial, using block randomization with a block size of 4.

Definitely yes;

Medication and placebo tablets were distributed in sealed opaque envelopes at the research unit, in sequential order, by a laboratory technician who was not directly involved with the study.

Definitely yes;

An independent, off-site clinical trials pharmacist masked and blinded the 25-mg prednisolone tablet and an identical placebo tablet to double-blind the study from the investigator and participants.

Probably no;

For the measurements at later time points, loss to follow-up was considerable and uneven between the study groups.

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

Some concerns for outcomes at longer follow-up.

Van Zele, 2010

Probably yes;

Reason: assumed but not specified.

Probably yes;

Reason: Eligible patients were randomly assigned to 3 groups by individuals not involved in the study. Study medication was provided in in unlabeled capsules.

Definitely yes;

Study personnel

and participants were blinded for the duration of the study.

Probably no;

For the measurements at later time points, loss to follow-up was considerable and uneven between the study groups.

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

Some concerns for outcomes at longer follow-up.

Hissaria, 2006

Probably yes;

Reason: assumed but not specified.

Definitely yes;

Patients were randomized by the hospital pharmacy to receive the study

medication, which consisted of prednisolone or placebo and were blinded to their treatment status.

Definitely yes;

Patients were

blinded to their treatment status and observers of imaging were blinded to treatment status.

Definitely yes;

Loss to follow-up was limited and similar between the groups.

Probably yes;

Reason: All relevant outcomes were reported

Probably yes;

Reason: No other problems noted

LOW