Interventional procedure overview of corticosteroid-releasing bioabsorbable stent or spacer insertion during endoscopic sinus surgery for chronic rhinosinusitis

Population and studies description

This interventional procedures overview is based on 4,897 people with CRS from 2 systematic reviews (Goshtasbi 2019, Zhang 2021), 1 retrospective cohort study (Hoffman 2023), 4 randomised controlled trials (Huang 2022, Samarei 2022, Wierzchowska 2021, Wang 2023), 1 prospective cohort before-after study (Pou 2017), and 2 case reports (Shipman 2022, Tang 2019). It also includes a review of adverse events reported on the US FDA MAUDE database (Shah 2022). This is a rapid review of the literature, and a flow chart of the complete selection process is shown in figure 1. This overview presents 11 studies as the key evidence in table 2 and table 3, and lists 52 other relevant studies in appendix B, table 5.

The systematic review by Goshtasbi et al. (2019) included a meta-analysis of 7 studies, all of which were described as randomised controlled trials. The methodology was compliant with the PRISMA guidelines. The SES implants were placed in the frontal or ethmoid sinuses. Of the 6 studies that described intraoperative insertion of the SES, all used intrapatient controls. The remaining study described in-office placement of a stent after ESS, which is not within the remit of this overview. Most of the reported primary outcomes were based on 1month data. Overall, the mean age ranged between 42 and 51 years and females comprised 34% to 68% of the cohorts. The proportion of people with polyps ranged from 16 to 76%. Of the 7 studies, 6 prescribed a 10- or 14-day course of antibiotics postoperatively and 1 study prescribed daily doses of steroid nasal spray. Some studies permitted additional postoperative treatment, such as corticosteroids for asthma control.

The systematic review by Zhang et al. (2021) was conducted as per PRISMA guidelines and included 8 randomised controlled trials in a qualitative analysis. The trials compared absorbable nasal packing impregnated with steroids against absorbable nasal packing alone, inserted during ESS. Sample sizes of the included studies ranged between 19 and 80 people. Of the 8 trials, 5 included only people with polyps, 2 included people with or without polyps and 1 included only people without polyps. All 8 included studies described the use of saline irrigation, topical steroids, and systemic antibiotics after the procedure. The follow up periods were up to 12 months.

The cohort study by Hoffman et al. (2023) aimed to assess the impact of using SES on healthcare resource use in the US, during the 2 years after surgery. It was a retrospective observational study using multisource databases containing healthcare claims and electronic medical record data in the US. People who had ESS with an SES were matched with those who had ESS without an implant using propensity scores. The overall cohort was subdivided according to the presence or absence of polyps. The mean age of the whole cohort was 48 years and 52% were female. The specific sinuses where the implants were placed was not reported.

Two randomised controlled trials were based in China and used intrapatient controls. The trial by Huang et al. (2022) included 181 people who had implants placed in the ethmoid sinus after bilateral ethmoidectomy. An SES was placed in the treatment side and synthetic absorbable packing material without steroids was placed in the control side. The primary outcome was the rate of postoperative interventions within 30 days. The mean age of the study population was 42 years, 29% were female and 96% had polyps. Efficacy outcomes were reported up to 90 days after the procedure and adverse events were recorded up to a year. After the ESS, a 7‑day course of antibiotics was offered. Nasal saline irrigation and oral mucolytics were routinely used during the follow-up period. Intranasal steroid sprays were allowed starting 30 days after the ESS. The trial by Wang et al. (2023) included 95 people who had 1 side randomised to have 1 SES implanted in the ethmoid sinus and if possible, another in the frontal sinus, whereas the contralateral side had surgery alone. The primary outcome was the Lund-Kennedy endoscopic score within 12 weeks of the surgery. Everyone in the study population had polyps, the mean age was 48.8 years and 52% were male. The follow up period was 12 weeks. After the ESS, prescribed nasal steroid sprays were permitted, but oral corticosteroids were not allowed up to week 12. Patients were instructed to use sprays or irrigation during the follow-up period.

The randomised controlled trial by Samarei et al. (2022) included 104 people, all with polyps, who had bilateral ESS. The middle meatus of each nostril was packed with either steroid-impregnated gelatine sponge or saline-impregnated gelatine sponge. The packing was suctioned from the middle meatus after 7 days. Of the 104 people, 27% were female and the mean age was 46 years. Postoperative oral antibiotics were offered for 14 days. Nasal saline irrigation and intranasal topical corticosteroid spray were resumed from 24 hours after the packing was removed. Follow up was 18 months.

The randomised controlled trial by Wierzchowska et al. (2021) included 120 people with or without polyps who had bilateral ESS. A biodegradable synthetic polyurethane foam soaked with antibiotic, steroid or both was inserted into the treatment side and the same packing soaked with saline was inserted into the control side. The mean age of the study population was 44.7 years and 41% were women. After the surgery, everyone was advised to rinse the nose with saline solution once a day for 2 weeks and to use a nasal steroid for 3 weeks. Follow up was 180 days.

The prospective cohort study by Pou et al. (2017) aimed to assess how the severity of inflammation before the procedure affected the outcomes. It included 136 people who had an SES implanted in 1 or both ethmoid sinuses. Of the total study population, 37% had polyps, 60% were female and 52% were aged over 50. The follow up period was 6 months.

Shah et al. (2022) is a review of the FDA MAUDE database, describing adverse events reported in association with use of the PROPEL SES. The MAUDE database includes mandatory reports from manufacturers and device importers when a device may have caused injury to a patient, and voluntary reports from other sources including healthcare professionals and patients. Limitations of the database include under-reporting, duplicate reporting, incomplete reports and uncertainty if the device caused the complication being described. The true denominator for these events is not captured and the database is not designed to calculate or compare complication rates.

The 2 case reports describe adverse events associated with the procedure that have not been reported elsewhere. One is a case of non-invasive fungal sinusitis (Shipman 2022) and the other describes the introduction of an SES through a dural defect (Tang 2019).

Table 2 presents study details.

Procedure technique

Several different bioabsorbable stents or spacers were used across the studies. Where it was specified, most were placed in the ethmoid sinuses. In the systematic review by Goshtasbi et al. (2019), the devices used were Propel Mini, Propel Contour and an unnamed SES (Intersect ENT) and Sinuband FP (BioInspire Technologies Inc.). The implants were placed in the ethmoid or frontal sinuses. The prospective cohort study by Pou et al. (2017) used the Propel SES implanted in the ethmoid cavity, and the review by Shah et al. (2022) was also focused on the Propel SES. The retrospective cohort study by Hoffman et al. (2023) did not specify the type of SES or the sinus in which the SES was placed. In 2 of the randomised controlled trials, a bioabsorbable SES from Puyi Biotechnology (China) was implanted in the ethmoid sinus (Huang 2022, Wang 2023). The systematic review by Zhang et al. (2021) included studies that used a synthetic proprietary bioabsorbable polymer (Nasopore), bioabsorbable gels and calcium alginate packing. Of the 8 included studies, 4 applied triamcinolone as the active steroid, the remaining studies applied betamethasone furoate, budesonide, mometasone furoate, and dexamethasone. The randomised controlled trial by Samarei et al. (2022) used an absorbable gelatine sponge impregnated with steroid (Gelfoam, Pharmacia and Upjohn Company, US) inserted into the middle meatus. The randomised controlled trial by Wierzchowska et al. (2021) used Nasopore soaked with antibiotic, steroid or both.

Efficacy

SNOT-22 score

SNOT-22 was reported as an outcome in 2 studies. In the prospective cohort study of 136 people, the mean score improved from 45.5 at baseline to 18.8 at 3 months (p<0.001) and 16.5 at 6 months (p<0.001; Pou 2017). In the systematic review by Goshtasbi et al. (2019), 1 study of 18 people reported an improvement in SNOT-22 scores from 52 at baseline to 19 at 1- and 3-month follow-up (p value not reported).

Nasal symptoms

Nasal obstruction and nasal symptom score were reported as outcomes in 1 study. In the randomised controlled trial of 95 people who had ESS with a SES placed in 1 ethmoid sinus and surgery alone in the other ethmoid sinus, the mean nasal obstruction score at 8 weeks was 0.92 in the SES group and 1.35 in the control group (p<0.01). The mean total nasal symptom score (range 0 to 40) was 5.47 in the SES group and 6.41 in the control group (p=0.001; Wang 2023).

Nasal blockage measured on a VAS from 0 to 10 was reported as an outcome in 1 study. In the randomised controlled trial of 120 people who had absorbable nasal packing with steroid, antibiotic or both in the treatment side, and absorbable nasal packing with saline in the control side, the scores were higher in the control side at most timepoints. In the group who had steroid only in the treatment side, the difference was statistically significant at day 90 (0.62 compared with 1.16, p=0.033) and day 180 (0.44 compared with 0.85, p=0.019). In the group who had a combination of steroid and antibiotic in the treatment side, the difference was statistically significant at day 10 (2.25 compared with 3.43, p=0.005) and day 30 (1.39 compared with 2.34, p=0.022; Wierzchowska 2021).

Endoscopic evaluation scores

The Lund-Kennedy score was reported as an outcome in 4 studies. In the randomised controlled trial of 95 people who had ESS with a SES placed in 1 ethmoid sinus and surgery alone in the other ethmoid sinus, the mean Lund-Kennedy score was statistically significantly lower in the SES side at 4, 8 and 12 weeks compared with the control side. At 12 weeks, the score was 1.05 for the SES side and 2.05 for the control side (p<0.001) compared with 5.0 and 5.1, respectively, at baseline (Wang 2023). In the randomised controlled trial of 120 people who had absorbable nasal packing with steroid, antibiotic or both in the treatment side and absorbable nasal packing with saline in the control side, the Lund-Kennedy scores were higher in the control side at all timepoints from day 10 to day 180. The difference between steroid and control was only statistically significant at day 90. The difference between steroid combined with antibiotic and control was statistically significant at all timepoints (Wierzchowska 2021). In the cohort study of 136 people, the Lund-Kennedy score reduced from 6.56 at baseline to 1.71 at 6 months in people with polyps, and from 3.48 to 0.87 in people without polyps (between groups p<0.001 at baseline and p=0.032 at 6 months; Pou 2017). In the systematic review by Zhang et al. (2021), 1 study reported an improvement of 0.39 in the mean Lund-Kennedy score at 90 days (p=0.008) but there were no statistically significant differences at other timepoints.

The POSE score was reported as an outcome in 2 studies. In the systematic review by Zhang et al. (2021), 1 study described statistically significant mean score reductions of 1.5 at 7 days, 2.24 at 14 days, 1.22 at 3 months, and 1.30 at 6 months (p<0.05 on all occasions). Another study in the same review reported score reductions at 1 and 4 weeks that were not statistically significant and a statistically significant reduction of 3.06 at 8 weeks. In the randomised controlled trial of 104 people who had absorbable gelatine sponge impregnated with steroid or saline inserted in each middle meatus, the mean POSE score was statistically significantly lower in the treatment side compared to the control at 3 and 6 months after the procedure. The scores in both sides were statistically significantly reduced from baseline at 1 month and at all the follow up points to 18 months (Samarei 2022).

Frontal sinus ostia patency

In the systematic review of 444 people by Goshtasbi et al. (2019), a meta-analysis of 3 studies showed the OR for frontal sinus ostia patency was 2.53 (95% CI 1.61 to 3.97, p<0.001) for the SES group compared to the control group, at 1 or 3 month follow up. In the same review, the mean difference in frontal sinus ostia or ethmoid inflammation was ‑10.86 mm (p<0.001; 4 studies) and the mean difference in frontal sinus ostia diameter was 1.34 mm (p<0.001; 3 studies).

Crusting

Crusting was reported as an outcome in 2 studies. In the randomised controlled trial of 95 people who had ESS with a SES placed in 1 ethmoid sinus and surgery alone in the other ethmoid sinus, the mean crusting score was statistically significantly higher in the SES side at 2 weeks compared with the control side (1.53 compared with 0.98, p<0.001). At 12 weeks, the score was statistically significantly lower for the SES side than the control side (0.2 compared with 0.36, p<0.01; Wang 2023). In the randomised controlled trial of 120 people who had absorbable nasal packing with steroid, antibiotic or both in the treatment side and absorbable nasal packing with saline in the control side, the crusting scores were similar between the groups at all timepoints. The only statistically significant difference was between steroid and control at day 10 (0.60 compared with 0.73, p=0.025; Wierzchowska 2021).

Need for postoperative intervention

The need for postoperative intervention was reported as an outcome in 4 studies. In the systematic review by Goshtasbi et al. (2019), the OR for postoperative intervention was 0.45 (95% CI 0.33 to 0.62, p<0.001; 5 studies) for the SES group compared to the control group, at 1 month follow up in 4 of the 5 studies. The OR for postoperative surgery was 0.30 (95% CI 0.18 to 0.52, p<0.001; 4 studies) and the OR for postoperative oral steroids was 0.58 (95% CI 0.40 to 0.84, p=0.004; 3 studies).

In the cohort study of 3,418 people who had ESS with or without SES, repeat sinus surgery within 24 months was reported in 4% (63 out of 1,709) of those in the SES group and 5% (88 out of 1,709) of those in the control group (p=0.037). In the subgroup of people with polyps, the rate of repeat sinus surgery was 4% (31 out of 819) in the SES group and 6% (49 out of 819) in the control group (p=0.039). For people without polyps, the rate was 4% in both groups. The rate of sinus endoscopy procedures during follow up was 36% (615 out of 1,709) in the SES group and 45% (763 out of 1,709) in the control group (p<0.001) and the rate of sinus debridement was 43% (727 out of 1,709) in the SES group and 55% (932 out of 1,709) in the control group (p<0.001; Hoffman 2023).

The randomised controlled trial of 181 people who had bilateral ESS with a SES in 1 side and bioresorbable nasal dressing without steroid in the other side reported the need for debridement within 30 days of the procedure. When this was determined by clinical investigators, the rate was 34% (61 out of 181) in the SES group and 66% in the control group (120 out of 181; p<0.0001). When it was determined by a panel of 3 independent reviewers, the rate was 14% (23 out of 160) in the SES group and 75% (120 out of 160) in the control group (Huang 2022).

In the cohort study of 136 people, the rate of revision ESS was 2% (2 out of 136; Pou 2017).

Recurrent polyposis

Recurrence or formation of polyps after the procedure was reported as an outcome in 2 studies. In the systematic review by Goshtasbi et al. (2019), the OR for recurrent polyposis was 0.42 (95% CI 0.25 to 0.74, p=0.002; 3 studies) for the SES group compared to the control group, at 1 month follow up. In the randomised controlled trial of 181 people, polyp formation within 30 days was reported in 23% (41 out of 181) of the sinuses with SES and 54% (98 out of 181) of the control sinuses (p<0.0001). At 90 days, the rates were 7% (8 out of 118) in the SES group and 25% (30 out of 118) in the control group (p<0.0001; Huang 2022).

Adhesions or scarring

The presence of adhesions or scarring after the procedure was reported as an outcome in 3 studies. In the systematic review by Goshtasbi et al. (2019), the OR for moderate to severe adhesions or scarring was 0.28 (95% CI 0.13 to 0.59, p<0.001; 3 studies) for the SES group compared to the control group, at 1 month follow up. In the randomised controlled trial of 181 people, severe adhesions within 30 days was reported in 1% (1 out of 181) of the sinuses with SES and 2% (4 out of 181) of the control sinuses (p=0.083). At 90 days, the rates were 8% (9 out of 118) in the SES group and 25% (30 out of 118) in the control group (p=0.0003; Huang 2022). In the randomised controlled trial of 95 people, mean scarring scores were 0.26 in the SES group and 0.41 in the control group at 4 weeks (p<0.05) and 0.3 in the SES group and 0.73 in the control group at 12 weeks (p<0.001; Wang 2023).

Hospital visits during follow up

The number of hospital visits after the procedure was reported in the cohort study of 3,418 people, based in the US. The rate of all-cause outpatient visits was 89% (1,528 out of 1,709) in the SES group and 94% (1,606 out of 1,709) in the control group (p<0.001). The rate of all-cause otolaryngologist visits was 59% (1,003 out of 1,709) in the SES group and 75% (1,289 out of 1,709) in the control group (p<0.001; Hoffman 2023).

Safety

Few of the studies reported any safety outcomes.

In the randomised controlled trial of 181 people, there were 26 adverse events that were judged by clinical investigators as having an indeterminate or unrelated relationship to the sinus stent and steroids (including nasal pain, nose bleeding, headache, acute rhinosinusitis). There were no statistically significant differences in intraocular pressure and lens opacities between the baseline and at postoperative days 14, 30, and 90 (Huang 2022).

Adverse events reported on the FDA MAUDE database

The review by Shah et al. (2022) searched the FDA MAUDE database for reports associated with a specific SES (Propel, Intersect ENT, US). It identified 25 medical device reports between 2012 and 2020, describing 40 adverse events. Although the denominator for this is unknown, the authors noted that 350,000 people have had a Propel SES implanted since 2011. The following adverse events or device malfunctions were identified:

Case reports

Two case reports of adverse events associated with the procedure were identified. The first described non-invasive fungal sinusitis that was diagnosed 2 weeks after a revision ESS. This was successfully treated by a left-sided revision maxillectomy, ethmoidectomy, and frontal sinusotomy (Shipman 2022). The second case report described someone who developed headache, confusion and nausea after ESS with insertion of multiple SES. Exploratory surgery showed that 1 of the SES was protruding through a dural defect. The SES was extracted, a frontal sinusotomy was done and the dural defect was repaired. After surgery, the patient's mental status returned to baseline and he was doing well a year later (Tang 2019).

Validity and generalisability

Any ongoing trials