Rader 2017.
| Methods | Randomised 1:1 with stratification by lesion size (coverage of ≤ 50% of cervix or >50%) and severity (CIN 3 versus CIN 2/3). Enrollment June 2005 through April 2012. | |
| Participants | 130 woman 18 years or older with CIN 3 verified on central pathology review and a visible lesion present by colposcopy after initial biopsy. Exclusion criteria included adenocarcinoma in situ, pregnancy, allergy to sulphonamides, history of cardiovascular disease or uncontrolled hypertension, and renal or hepatic disorders. Multicentre trial. | |
| Interventions | Celecoxib 400 mg daily or placebo. Baseline exam with colposcopy, serum sample, and cervical swabs were obtained. Interval colposcopy repeated at 8 weeks. Treatment continued 14‐18 weeks. | |
| Outcomes | Primary endpoints were regression to CIN 1 or less and estimation of toxicity. Complete response was regression to normal tissue or squamous metaplasia. Partial response was regression to CIN 1. Progressive disease was development of squamous carcinoma and persistent disease was presence of CIN 2 or 3 or squamous carcinoma in‐situ after treatment. 67 patients were randomised to celecoxib with 63 receiving treatment and 50 having evaluable tissue. 63 were randomised to placebo with 58 receiving treatment and 41 having evaluable tissue. One grade 3 gastrointestinal adverse event was noted in the celecoxib group; otherwise, toxicity was similar between arms. Histological responses were present in 20/50 (40%) of the celecoxib arm versus 14/41 (34.1%) in the placebo group. With an ITT analysis, response rates were 20/67 (29.9%) and 14/63 (22.2%) for treatment and placebo. 31/81 (38%) response was noted if the lesion was less than 50% of the cervix versus 3/10 (30%) if greater than 50%. Response rates were similar if HPV‐16 was present or absent at 36.2% and 38.5%. Patients with high serum VEGF levels were more like to response to celecoxib versus placebo at 47.4% and 14.3%. | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Patients randomised in 1:1 fashion. |
| Allocation concealment (selection bias) | Low risk | Celecoxib and placebo supplied by Biologics Inc. |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Both physicians and patients blinded to treatment group. Translational biological sample analysis was also blinded. |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Both physicians and patients blinded to treatment group. Translational biological sample analysis was also blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | There was a loss of 30% of the patients; however, the larger number of women enrolled reduces the risk for attrition bias. Data were analysed both on patients completing the study and as ITT analysis. |
| Selective reporting (reporting bias) | Unclear risk | Insufficient information |
| Other bias | Unclear risk | Insufficient information |
ALT: alanine aminotransferase AST: aspartate aminotransferase CIN: cervical intraepithelial neoplasia HPV: human papillomavirus ITT: intention‐to‐treat LEEP: loop electrosurgical excision procedure NSAID: non‐steroidal anti‐inflammatory agent VEGF: vascular endothelial growth factor