Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Wallwork, 2016

Type of study:

Randomized controlled trial

Setting and country: multicentre, Australia

Funding and conflicts of interest:

Not reported

Inclusion criteria:

aged greater than 18 years with a history consistent with the diagnosis of chronic rhinosinusitis as outlined by the Rhinosinusitis Task Force

Exclusion criteria:

- a history of cystic fibrosis, primary ciliary dyskinesia, immune deficiency, allergic fungal sinusitis, nasal polyposis, and

impairment of liver or renal function.

- Pregnant and breastfeeding

women

- those taking medications with a

known adverse interaction with macrolides or with a history of macrolide hypersensitivity.

- if topical or systemic corticosteroids within 4 weeks

of entering the study.

N total at baseline:

Intervention: 29

Control: 35

Important prognostic factors²:

Not reported

Groups comparable at baseline? Unknown

Describe intervention (treatment/procedure/test):

Roxithromycin 150mg daily for 12 weeks

Describe  control (treatment/procedure/test):

Placebo daily for 12 weeks

Length of follow-up:

3 months

Loss-to-follow-up:

Intervention:

2 (6.9%)

Reasons

Developed nausea and vomiting (n=1)

Lost to follow-up (n=1)

Control:

3 (8.6%)

Reasons:

Lost to follow-up (n=1)

Developed a rash (n=1)

Developed abdominal pain (n=1)

Incomplete outcome data:

Not reported

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

1. SNOT score, mean ± SD:

I: 2.34 ± 1.02

C: 2.88 ± 0.71

SMD: -0.62 (-1.12 to -0.11)

2. Total symptom score

Not reported

3. Nasal polyp score

Not reported

4. Adverse events

Not reported

Authors conclusion:

These findings suggest that macrolides may have a beneficial role in the treatment of chronic rhinosinusitis, particularly in patients with

low levels of IgE, and supports the in vitro evidence of

their anti-inflammatory activity. Additional studies are required to assess their place in clinical practice.

Videler, 2011

Type of study:

Randomized controlled trial

Setting and country: multicentre, six different countries (the Netherlands, Finland, Belgium, United Kingdom, Sweden, Croatia

Funding and conflicts of interest:

The Azitromycin and placebo used in this study was kindly

provided by PLIVA HRVATSKA d.o.o., Zagreb, Croatia.

No conflict of interest

Inclusion criteria:

Patients between 18 and 70 years of age

Met the CRS criteria outlined in the EPOS definition for moderate-to-severe CRS

Exclusion criteria:

Patients with a known history of hypersensitivity to macrolides, or those using medication known to have had a reaction to members of the macrolide family

N total at baseline:

Intervention:  29

Control: 31

Important prognostic factors²:

Medium age, years:

I: 49

C: 49

Ratio male to female:

I: 17:12

C:  13:18

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Azithromycin 500mg weekly for 12 weeks

Describe  control (treatment/procedure/test):

Placebo weekly for 12 weeks

Length of follow-up:

24 weeks

Loss-to-follow-up:

Intervention:

3 (10.3%)

Reasons

Stomach pain (n=1)

Pregnancy (n=1)

Did not attend follow-up at 14 weeks (n=1)

Control:

4 (12.9%)

Reasons

Pneumonia treated with antibiotics (n=1)

Did not attend follow-up at 12 weeks (n=1)

ESS performed because of progress of the sinonasal complaints (n=1)

Did not attend follow-up at 14 weeks (n=1)

Incomplete outcome data:

Not reported

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

1. SNOT score, mean ± SD:

I: 2 ± 1.34

C: 1.48 ± 0.88

SMD: 0.46 (-0.08 to 0.99)

2. Total symptom score

Not reported

3. Nasal polyp score

Not reported

4. Adverse events

I:

mild gastrointestinal complaints (n=2)

Headache (n=1)

C:

mild gastrointestinal complaints (n=2)

Headache (n=1)

Authors conclusion:

At the investigated dose of AZM over 3 months, no significant benefit was found over placebo. Possible reasons could be disease severity in the investigated group, under-dosage of AZM and under-powering of the study. Therefore, more research is urgently required.

Maniakas, 2021

Type of study:

Randomized controlled trial

Setting and country: single centre, Canada

Funding and conflicts of interest:

Funding sources for the study: Canadian Institutes of Health Research (to

A.M.); Fonds de Recherche du Québec-Santé; Pfizer Canada (unrestricted

investigator-initiated grant to A.M. and M.D.).

Potential conflicts of interest: M.D. has received research funding from GSK,

AstraZeneca, and Sanofi/Regeneron; is on the speaker’s bureau for

AstraZeneca and MEDA; and is founder, owner, and president of Probionase

Therapies. The remaining authors declare no conflicts of interest.

Inclusion criteria:

≥18 years of age, had a diagnosis of CRS,25 and had at least 1 of the criteria used

to qualify a patient at high risk of disease recurrence, including: history of previous sinus surgery; sinus surgery at ≤38 years of age; absolute eosinophilia ≥500 cells/mm; total serum IgE levels ≥150 kIU/L; sinus culture of a Gramnegative organism at any time-point; and intraoperative

finding of eosinophilic mucin.

Exclusion criteria:

- patients who had received topical or systemic antibiotics up to 4 weeks before ESS.

- patients with immunodeficiencies, cystic fibrosis, inverted papilloma, osteoma, cystic masses, mucoceles, or any other sinonasal tumors

- Patients with any known level of

cardiovascular disease

N total at baseline:

Intervention: 24

Control: 24

Important prognostic factors²:

Mean age (range), years:

I: 50 (25-75)

C: 44 (20-66)

Sex:

I: 38% M

C: 67% M

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

250 mg AZI, 3 times per week

Describe  control (treatment/procedure/test):

Placebo

Length of follow-up:

4 months

Loss-to-follow-up:

None

Incomplete outcome data:

Not reported

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

1. SNOT-22 score, mean (range):

Visit 3

I: 26.1 (3 –78)

C: 29.7 (6-89)

Improvement

I:18

C: -0.9

2. Total symptom score

Not reported

3. Nasal polyp score

Not reported

4. Adverse events, n:

I: 0

C: 0

Authors conclusion:

Low-dose azithromycin is a therapeutic option with few side effects. Its use can show favourable clinical outcomes in this difficult-to-treat population, especially if patients are AERD-negative.

Haxel, 2014

Type of study:

Randomized controlled trial

Setting and country: single centre, Germany

Funding and conflicts of interest:

The authors have no funding, financial relationships, or conflicts of interest to disclose.

Inclusion criteria:

Patients of both genders over 18 years of age who had underwent endonasal sinus surgery because of CRS 2 weeks earlier

Exclusion criteria:

single-sided CRS, cystic fibrosis, immunodeficiency, primary cilia dysfunction, hypersensitivity to macrolides, liver or renal deficiency, cardiac arrhythmia, QT- time elongation on electrocardiogram, pregnancy, and concomi- tant medication with drugs interacting with macrolides.

N total at baseline:

Intervention: 29

Control: 29

Important prognostic factors²:

age ± SD:

I: 45.7 (6 12.8)

C: 47.7 (6 12.5)

Sex:

I: 59% M

C: 59% M

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

Erythromycin 250mg once daily for 12 weeks +

fluticasone fuorate 27.5 mcg once daily

Describe  control (treatment/procedure/test):

Placebo +

fluticasone fuorate 27.5 mcg once daily

Length of follow-up:

24 weeks

Loss-to-follow-up:

Intervention:

8 (27.6%)

Reasons (describe)

Refuse participation (n=1)

Lost to follow-up (n=6)

Stop medication due to other diagnosis (n=1)

Control:

2 (6.9%)

Reasons (describe)

Refuse participation (n=1)

Lost to follow-up (n=1)

Incomplete outcome data:

Not reported

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

1. SNOT score, mean ± SD:

I: 0.95 ± 0.13

C: 0.79 ± 0.14

SMD: 1.17 (0.61 to 1.73)

2. Total symptom score

Not reported

3. Nasal polyp score

Not reported

4. Adverse events

Not reported

Authors conclusion:

A general recommendation for long-term, low-dose erythromycin treatment after surgery for CRS cannot be given. In patients with CRS without nasal polyps, a tendency to improved parameters was detected.

Amali, 2015

Type of study:

Randomized controlled trial

Setting and country: single centre, Iran

Funding and conflicts of interest:

Funding not reported

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

Inclusion criteria:

Patients with >3 months of CRS symptoms and endoscopic signs and/or changes on computed tomography (CT) and who did not respond to the standard treatment regimes, including nasal saline solution irrigation combined with intranasal corticosteroids and antibiotics, and were candidates for ESS

Exclusion criteria:

previous sinus surgery, hypersensitivity to macro- lides, use of drugs suspected of having interactions with macrolides, cystic fibrosis, congenital mucociliary problems, immune deficiency, systemic vasculitis, severe septal deviation, and craniofacial malfor- mation. Patients who had used systemic antibiotics and/or systemic corticosteroids within 4 weeks of the study or throughout the study were excluded.

N total at baseline:

Intervention: 22

Control: 44

Important prognostic factors²:

age ± SD:

I: 34.9 (9.2)

C: 39.1 (10.7)

Sex:

I: 63.6% M

C: 72.7% M

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

Azithromycin 250 mg once daily for 12 weeks  +

All patients received fluticasone proprioanate 100 mcg twice daily

Describe  control (treatment/procedure/test):

Placebo

All patients received +fluticasone proprioanate 100 mcg twice daily

Length of follow-up:

12 weeks

Loss-to-follow-up:

I Intervention:

2 (9,1%)

Reasons (describe)

Not reported

Control:

4 (9.1%)

Reasons (describe)

Not reported

Incomplete outcome data:

Not reported

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

1. SNOT score, mean ± SD:

I: 0.27 ± 0.12

C: 0.46 ± 0.29

SMD: -0.76 (-1.31 to -0.20)

2. Total symptom score

Not reported

3. Nasal polyp score

Not reported

4. Adverse events

No serious adverse event, including angioedema, anaphy- laxis, and cholestatic jaundice, was reported.

Authors conclusion:

Treatment with long-term low-dose azithromycin in combination with the conventional therapy could statistically reduce the recurrence rate of CRS symptoms after functional endoscopic sinus surgery, but there was not sufficient evidence to support clinical significance of azithromycin at the investigated dose. Further larger scale trials, along with a longer follow-up period, is needed to evaluate the effectiveness of the therapy.

Wu, 2019

Type of study:

Randomized controlled trial

Setting and country: single centre, Taiwan

Funding and conflicts of interest:

Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article

Funding not reported

Inclusion criteria:

CRS patients who responded poorly to medical treatment, and subsequently underwent standard bilateral FESS

Exclusion criteria:

Any patient who suffered from an acute flare of rhinosinusitis and needed other antibiotics for management

N total at baseline:

Intervention: 35

Control: 37

Important prognostic factors²:

For example

age ± SD:

I: 45.63 ± 13.22

C: 49.35 ± 12.24

Sex:

I: 42.9% M

C: 43.2% M

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

oral erythromycin (250mg, twice a day) for 12 weeks

Describe  control (treatment/procedure/test):

intranasal steroid (mometasone furoate nasal spray, 4 puffs, once a day) for 12 weeks

Length of follow-up:

3 months

Loss-to-follow-up:

None

Incomplete outcome data:

Not reported

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

1. (TW)SNOT score, mean ± SD:

Pretreatment

I: 27.8 ± 18.7

C: 23.3 ± 18.6

Posttreatment:

I: 27.6 ± 22.9

C: 21.5 ± 18.2

2. Total symptom score

Not reported

3. Nasal polyp score

Not reported

4. Adverse events

5. Smell threshold

Pretreatment

I: −4.20 ± 3.44

C: −4.32 ± 3.19

Posttreatment:

I: −5.06 ± 3.50

C: −4.67 ± 3.19

Authors conclusion:

Our study showed that long-term, low-dose erythromycin treatment improved the endoscopic score, smell thresh- old, and saccharine transit time in patients with persistent rhinosinusitis after FESS.

Ragab, 2004,2010

Type of study:

Randomized controlled trial

Setting and country: single centre, United Kingdom

Funding and conflicts of interest: Not reported

Inclusion criteria:

patients with CRS

Exclusion criteria:

pregnancy, lactation, significant psychologic prob- lems, inability to comply with study protocol, children under 18 years of age, systemic diseases affecting the nose (e.g., Wegener’s granulomatosis, sarcoid, primary ciliary dyskinesia, cystic fibro- sis, and acute upper or lower respiratory tract infections within 2 weeks before the inclusion visit), use of systemic corticosteroids within 4 weeks before the inclusion visit, systemic diseases pre- venting participation in the study, and medical or surgical treat- ments influencing the study.

N total at baseline:

Intervention: 45

Control: 44

Important prognostic factors²:

age ± SD:

43 years

Sex:

50% M

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Erythromycin 500mg bid x 2 weeks then 250mg bid + alkaline douche + intranasal corticosteroid x 10 weeks

Describe  control (treatment/procedure/test):

Surgery + erythromycin 250mg bid x 2 weeks + alkaline douche + intranasal corticosteroid (after 2

weeks)

Length of follow-up:

12 months

Loss-to-follow-up:

Intervention:

7 (15.6%)

Reasons:

Patients unavailable (n=7)

Control:

5 (11.1%)

Reasons:

Did not receive the treatment (n=1)

Patients unavailable (n=4)

Incomplete outcome data:

Not reported

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

1. SNOT score at 12 months, mean ± SD:

I: 1.1 ± 1

C: 1.1 ± 0.98

2. Total symptom score

Not reported

3. Nasal polyp score

Not reported

4. Adverse events

I: 3 patients

C: 4 patients

Authors conclusion:

Both maximal medical and surgical therapy of CRS improve the quality of life of CRS patients, providing further evidence that chronic rhinosinusitis should be targeted with maximal medical therapy in the first instance, with surgical treatment being reserved for cases refractory to medical therapy. The presence of nasal polyps is not associated with any negative effect on the quality of life after CRS therapy, either medical or surgical.

Peric, 2014

Type of study:

Randomized controlled trial

Setting and country: single centre, Serbia

Funding and conflicts of interest:

This investigation was supported by grants from the Military Medical Academy Research Fund. It was performed as part of a project of the Institute of Medical Research, Faculty of Medicine, Military Medical Academy, Belgrade, Serbia (VMA/11-14/B-6). The authors declare no conflict of interests.

Inclusion criteria:

patients with nasal polyposis

Exclusion criteria:

history of paranasal sinus surgery before enrolment

N total at baseline:

Intervention: 40

Control: 40

Important prognostic factors²:

age ± SD:

I: 44.28 ± 13.05

C: 43.30 ± 12.16

Sex:

I: 65% M

C: 63% M

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Clarithromycin 500mg daily x 8 weeks followed by surgery

Describe  control (treatment/procedure/test):

Surgery alone

Length of follow-up:

12 months

Loss-to-follow-up:

No lost to follow-up reported

Incomplete outcome data:

Not reported

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

1. SNOT score, mean ± SD:

Not reported

2. Total symptom score, NSSt12 minus NSSt6, mean± SD:

I: 2.93 ± 2.63

C: 1.58 ± 3.66

P=0.069

3. Nasal polyp score

Not reported

4. Adverse events

I: 4 patients

C: 7 patients

Authors conclusion:

Preoperative clarithromycin administration postponed nasal polyp relapse after FESS. Allergies have no influence on the clinical efficacy of clarithromycin therapy and on the efficacy of FESS.

Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Huang,

2019

[individual study characteristics deduced from [Huang,

2019

]

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of RCTs

Literature search up to December 30, 2017

See table 1 for study characteristics included studies.

Study design: RCT

Setting and Country: China

Source of funding and conflicts of interest:

Potential conflict of interest: None provided.

Funding not reported

Inclusion criteria SR:

(1) adult patients (age &18 years old) with CRSwNP or CRSsNP according to the def- inition from the latest 2013 Chinese CRS guideline15 or the EPOS201214; (2) the study design should be an RCT;

(3) comparisons included the combination of oral clar- ithromycin and nasal glucocorticoid spray with or with- out nasal saline irrigation vs nasal glucocorticoid spray with or without nasal saline irrigation alone, oral clar- ithromycin vs nasal glucocorticoid spray, or high-dose oral clarithromycin vs low-dose oral clarithromycin; (4) studies were published in English or Chinese.

Exclusion criteria SR:

Nonrandomized and quasirandomized trials.

no clear description of randomization methods, or those assessing cost-effectiveness of relevant interven- tions only

17 studies included

Important patient characteristics at baseline:

See table 1 for study characteristics included studies.

Groups comparable at baseline? Yes

Describe intervention:

See table 1 for study characteristics included studies.

Describe  control:

See table 1 for study characteristics included studies.

End-point of follow-up:

See table 1 for study characteristics included studies.

For how many participants were no complete outcome data available?

Not reported

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

1. Quality of life:

Not reported

2. Total symptom score VAS score, mean difference (95% CI):

adding oral clarithromycin to nasal glucocorticoid spray with or without nasal saline irrigation

Short term

–0.48; 95% CI, 1.24 to 0.29

Medium term

–0.85; 95% CI, –1.42 to –0.29

oral clarithromycin vs nasal glucocorticoid spray

Short term

0.22; 95% CI, –2.08 to 2.52

Medium term

0.11; 95% CI, –0.49 to 0.70

3. Nasal polyp score

Not reported

4. Adverse events, RR (95% CI)

adding oral clarithromycin to nasal glucocorticoid spray with or without nasal saline irrigation (12 weeks or 3 months)

1.50; 95% CI, 0.26 to 8.60

Authors conclusion:

For the treatment of CRS, adding oral clarithromycin to intranasal steroid spray with or without nasal saline irrigation may achieve better results than using intranasal steroid spray with or without nasal saline irrigation. There is insufficient evidence to confirm that oral clarithromycin alone may have similar efficacy as nasal glu-cocorticoid spray alone. High-quality evidence in this area is needed.

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

Wallwork, 2016

Probably yes;

Reason: After recruitment into the study, subjects were randomized by the pharmacy department, using a random number table

Probably yes;

Reason: After recruitment into the study, subjects were randomized by the pharmacy department, using a random number table

Probably yes;

Reason: Patients and investigators were kept blinded to the randomization until the completion of the study.  (blinding of data collectors and analysts not reported)

Probably yes;

Reason: Loss to follow-up was infrequent in intervention and control group.

Definitely yes;

Reason: All relevant outcomes were reported

Definitely yes;

Reason: No other problems noted

LOW

Videler,2011

Probably yes;

Reason: The randomized, numbered study medication was kindly pro- vided by the pharmaceutical company PLIVA (Zagreb, Croa- tia). Study medication was allocated per centre in two randomized blocks, containing six packs of treatments each.

Probably yes;

Reason: The randomized, numbered study medication was kindly pro- vided by the pharmaceutical company PLIVA (Zagreb, Croa- tia). Study medication was allocated per centre in two randomized blocks, containing six packs of treatments each.

Probably yes;

Reason: Double-blind studydesign.

(blinding of data collectors and analysts not reported)

Probably yes;

Reason: Loss to follow-up was infrequent in intervention and control group.

Definitely yes

Reason: All relevant outcomes were reported;

Definitely yes;

Reason: No other problems noted

LOW

Maniakas, 2021

Definitely yes

Reason: Block randomization in groups of 4 was per- formed by the institution’s research pharmacy.

Probably yes

Reason: Block randomization in groups of 4 was per- formed by the institution’s research pharmacy.

Definitely yes

Reason: Both patients and investigators were blinded to the assigned drug.

Probably yes;

Reason: Loss to follow-up was infrequent in intervention and control group.

Definitely yes;

Reason: All relevant outcomes were reported

Definitely yes;

Reason: No other problems noted

LOW

Haxel, 2014

Definitely yes

Reason: A randomiza- tion list was generated by a computer program in the Interdisci- plinary Center for Clinical Trials and was confidentially stored in this institution.

Probably yes

Reason: A randomiza- tion list was generated by a computer program in the Interdisci- plinary Center for Clinical Trials and was confidentially stored in this institution.

Probably yes

Reason: Double-blind studydesign.

(blinding of data collectors and analysts not reported)

Probably no;

Reason: More lost to follow-up in intervention group, not specified

Definitely yes;

Reason: All relevant outcomes were reported

Definitely yes;

Reason: No other problems noted

SOME CONCERNS

Bias due to selective lost to follow-up

Ameli, 2015

Definitely yes

Reason: The study medications were randomized through block random- ization with 2:1 randomization design (block size of 6).

Probably yes

Reason: The patients, investigators, and individuals who analyzed the outcomes were unaware of the randomization schedule.

Definitely yes

Reason: The patients, investigators, and individuals who analyzed the outcomes were unaware of the randomization schedule.

Probably yes;

Reason: Loss to follow-up was infrequent in intervention and control group.

Definitely yes;

Reason: All relevant outcomes were reported

Definitely yes;

Reason: No other problems noted

LOW

Wu, 2019

Probably yes

Reason: Randomization assign- ments were generated by an independent statistician.

Probably yes

Reason: Randomization assign- ments were generated by an independent statistician.

Probably no

Reason: Unclear if the study was blinded

Probably yes;

Reason: Loss to follow-up was infrequent in intervention and control group.

Definitely yes;

Reason: All relevant outcomes were reported

Definitely yes;

Reason: No other problems noted

SOME CONCERNS

No blinding

Ragab, 2004

Ragab, 2010

Probably no;

Reason: Not specified how randomization took place.

“Thus, 90 patients were randomized for inclusion in the study and were randomized equally into either the medical or surgical group. “

Probably no;

Reason: Not specified how randomization took place.

“Thus, 90 patients were randomized for inclusion in the study and were randomized equally into either the medical or surgical group. “

Definitely no;

Reason: Not reported if there was blinding.

Probably yes;

Reason: Loss to follow-up was infrequent in intervention and control group.

Definitely yes;

Reason: All relevant outcomes were reported

Definitely yes;

Reason: No other problems noted

HIGH

Unknown randomization

No blinding

Peric, 2014

Probably no;

Reason: Not specified how randomization took place.

Probably no;

Reason: Not specified how randomization took place.

Definitely no;

Reason: Not reported if there was blinding.

Probably yes;

Reason: Loss to follow-up was infrequent in intervention and control group.

Definitely yes;

Reason: All relevant outcomes were reported

Definitely yes;

Reason: No other problems noted

HIGH

Unknown randomization

No blinding

Lechien, 2019

Definitely yes

Reason: Permuted block randomization method was applied to generate randomization codes. Consort guidelines for reporting randomized controlled trials (RCTs) were followed.

Probably yes

Reason: Permuted block randomization method was applied to generate randomization codes. Consort guidelines for reporting randomized controlled trials (RCTs) were followed.

Definitely no;

Reason: Not reported if there was blinding.

Probably no;

Reason: Reason for loss to follow-up was not stated

Definitely yes;

Reason: All relevant outcomes were reported

Definitely yes;

Reason: No other problems noted

SOME CONCERNS

No blinding

Reasons lost to follow-up not stated

Author and year

Reason for exclusion

N/A