ASPIRe: Apical Suspension Repair for Vault Prolapse in a Three-Arm Randomized Trial
ASPIRe was a nine-center, three-arm randomized trial with superiority and noninferiority hypotheses that compared sacrocolpopexy and Uphold LITE transvaginal mesh with transvaginal native-tissue repair in 376 women with symptomatic vault prolapse after total hysterectomy (360 operated), with time to composite failure through 36 months as the primary endpoint. Modeled 36-month failure was 28% after sacrocolpopexy, 29% after mesh and 43% after native-tissue repair; sacrocolpopexy was superior to native tissue (adjusted HR 0.57, 99% CI 0.33–0.98), mesh was noninferior to sacrocolpopexy, and mesh was not superior to native tissue after adjustment for multiple comparisons (adjusted HR 0.60, 99% CI 0.34–1.03).[1]
- Design and population
- Nine-center, three-arm, superiority and noninferiority randomized trial. Women aged 21 or older with symptomatic vaginal vault prolapse beyond the hymen after total hysterectomy; 376 randomized, 360 treated (arm sizes are treated participants).
- Arms
- Sacrocolpopexy with mesh versus transvaginal mesh (Uphold LITE) versus transvaginal native-tissue apical repair
- Report and follow-up
- 2024 · Analysis when the last participant reached 36 months (July 2022); 296/360 (82%) completed follow-up
| Endpoint | Results | Effect | Finding |
|---|---|---|---|
| Adjusted 36-month failure probability, sacrocolpopexy versus native-tissue repair (superiority, alpha 0.01, MITT-NTR population) | 28% vs 43% | HR 0.57; 99% 0.33–0.98; P 0.008 | Met |
| Adjusted 36-month failure probability, transvaginal mesh versus sacrocolpopexy (noninferiority, margin HR 1.93, alpha 0.03, per-protocol population) | 26% vs 27% | HR 1.05; P 0.01 | Met |
| Adjusted 36-month failure probability, transvaginal mesh versus native-tissue repair (superiority, alpha 0.01, MITT-NTR population) | 29% vs 43% | HR 0.6; 99% 0.34–1.03; P 0.02 | Not met |
| Step-down superiority test, transvaginal mesh versus sacrocolpopexy (alpha 0.03, modified intention-to-treat) | 27% vs 29% | HR 1.08; 97% 0.65–1.78; P 0.76 | Not met |
| Crude cumulative failure, modified intention-to-treat | 32% (38/119) vs 32% (37/116) vs 45% (55/123) | — | Descriptive |
Harms: Vaginal mesh exposure related to the apical procedure: 4/120 (3%) vs 6/115 (5%); Suture exposure 12 weeks after surgery: 6/120 (5%) vs 3/115 (3%) vs 17/125 (14%); Urinary tract infection: 17/120 (14%) vs 42/115 (37%) vs 43/125 (34%)
Design
Women aged 21 or older requested surgery for symptomatic prolapse beyond the hymen, with vault prolapse after total hysterectomy reaching at least the lower two-thirds of the vagina. Prior synthetic or biologic augmentation of prolapse repair in any compartment and prior sacrospinous ligament fixation excluded participants. Of 1,785 women screened, 391 consented and 376 were randomized 1:1:1 before surgery by permuted blocks stratified by site and age category (younger than 65 or 65 and older); 360 had surgery. Participants were masked to assignment until surgery was complete, and masked personnel performed all examinations, questionnaires and adverse event assessments from the 6-week visit. In April 2019 the US Food and Drug Administration halted sales of transvaginal mesh kits, and the five participants still awaiting mesh surgery were re-randomized 1:1 to sacrocolpopexy or native-tissue repair.[1]
Baseline characteristics were similar across arms. Mean age was 66.1 years (SD 8.7), 302/360 participants (83.9%) were White, and stage 3 prolapse affected 66% to 76% of each arm and stage 4 prolapse 6% to 10%. Prior prolapse surgery had been performed in 17% to 30% and prior incontinence surgery in 11% to 21% of each arm.[1]
Failure was the first occurrence of retreatment for prolapse (pessary or surgery), any POP-Q measure beyond the hymen, or any degree of bother from the Pelvic Floor Distress Inventory bulge question. The trial tested three prespecified comparisons: noninferiority of mesh to sacrocolpopexy (hazard ratio margin 1.93, alpha 0.03, per-protocol population), superiority of sacrocolpopexy to native tissue (alpha 0.01) and superiority of mesh to native tissue (alpha 0.01), with a step-down superiority test of mesh against sacrocolpopexy if noninferiority held. The margin corresponded to a 15-point difference in 2-year failure risk (35% versus 20%). Enrolling 121 per arm gave 85% power for noninferiority and 93% power for each superiority comparison, assuming 2-year failure of 20% with either mesh repair and 40% with native tissue. Superiority analyses used the modified intention-to-treat population. The model was an interval-censored proportional hazards model with piecewise exponential hazards over five periods, adjusted for site and age category; proportional hazards showed a mild departure (P = 0.04).[1]
Results
Adjusted 36-month failure was 43% (95% CI 35%–53%) with native-tissue repair, 28% (95% CI 20%–37%) with sacrocolpopexy and 29% (95% CI 21%–38%) with transvaginal mesh. Sacrocolpopexy was superior to native tissue (adjusted HR 0.57, 99% CI 0.33–0.98; P = 0.008). Mesh did not reach the adjusted threshold against native tissue (adjusted HR 0.60, 99% CI 0.34–1.03; P = 0.02), although it did in the supportive per-protocol analysis (adjusted HR 0.57, 99% CI 0.32–1.00; P = 0.01). Mesh was noninferior to sacrocolpopexy in the per-protocol population (adjusted HR 1.05; upper one-sided 97% confidence limit 1.65, below the 1.93 margin), and the step-down test found it not superior (adjusted HR 1.08, 97% CI 0.65–1.78; P = 0.76). Crude cumulative failure was 32% (38/119) after sacrocolpopexy, 32% (37/116) after mesh and 45% (55/123) after native tissue.[1]
Failure was usually anatomic only (52% to 63%) or symptomatic only (27% to 39%). Retreatment for prolapse was uncommon: 8/118 (7%) after native tissue, 5/120 (4%) after sacrocolpopexy and 3/113 (3%) after mesh (P = 0.33).[1]
Anatomic support favored sacrocolpopexy. The mean postoperative leading edge of prolapse was −1.4 cm after sacrocolpopexy, −0.9 cm after mesh (P = 0.03 versus sacrocolpopexy) and −0.6 cm after native tissue (P < 0.001 versus sacrocolpopexy). Total vaginal length was 1.1 cm longer after sacrocolpopexy than after native tissue and 1.3 cm longer than after mesh.[1]
Patient-reported outcomes improved in every arm. At 3 years, 88/93 women (95%) after sacrocolpopexy, 84/89 (94%) after mesh and 79/91 (87%) after native tissue reported being much or very much better (P = 0.12). Sacrocolpopexy and mesh improved global pelvic floor symptoms and the urinary subscale of the PFDI-20 more than native tissue, and sacrocolpopexy improved colorectal symptoms and the SF-12 mental score more than native tissue. Prolapse symptoms, general quality of life, decision regret and satisfaction did not differ. Of 360 participants, 152 (42%) were sexually active before surgery and 122/287 (43%) at 36 months; sexual function improved in all arms.[1]
In a planned analysis of 335 women (123 native tissue, 107 sacrocolpopexy, 105 mesh), body image improved by 6 months and stayed improved to 36 months with no difference among arms. Body image and sexual function changes were correlated among sexually active women (P < 0.001); 99 (30%) were sexually active at every visit and 131 (39%) at none.[2]
In a nested cohort of 146 women aged 65 or older (50 native tissue, 47 sacrocolpopexy, 48 mesh), prefrail or frail women (Robinson Frailty Index 2 or higher) had a shorter time to composite failure than nonfrail women (adjusted HR 2.1, 95% CI 1.2–3.6), and so did women with compromised mobility. Geriatric outcomes did not differ by frailty status, but prefrail or frail women who lived alone needed more help in the first 6 weeks (19% versus 6%; P = 0.04).[3]
Surgery and treatment delivery
Sacrocolpopexy could be open, laparoscopic or robotic: 69/113 operations (61%) were robotic, 26/113 (23%) laparoscopic and 18/113 (16%) open. Transvaginal mesh used the Uphold LITE support system (Boston Scientific). The native-tissue operation was either sacrospinous ligament fixation (110/134; 82%) or uterosacral ligament suspension (24/134; 18%), each placing two permanent and two delayed absorbable monofilament sutures in the vagina. More than three-quarters of vaginal operations included anterior colporrhaphy and two-thirds included posterior colporrhaphy or perineorrhaphy; full-length midurethral slings were permitted.[1]
Median operative time was 90 minutes shorter in the vaginal arms than with sacrocolpopexy, and blood loss was similar. Surgeons converted 7/129 sacrocolpopexies (5%) because of intra-abdominal adhesions (five to native tissue, two to mesh) and 5/121 mesh operations (4%) to native tissue (vaginal adhesions in one, cystotomy in four).[1]
Adverse events
Vaginal mesh exposure related to the apical procedure occurred in 4/120 women (3%) after sacrocolpopexy and 6/115 (5%) after transvaginal mesh. Twelve weeks after surgery, suture exposure was more frequent after native tissue (17/125; 14%) than after sacrocolpopexy (6/120; 5%) or mesh (3/115; 3%; P = 0.02). One participant in each transvaginal arm needed reoperation for exposure, of suture after native tissue and of mesh after transvaginal mesh.[1]
Urinary tract infection affected 17/120 (14%) after sacrocolpopexy, 42/115 (37%) after mesh and 43/125 (34%) after native tissue (P < 0.001). Return to the operating room during the initial hospitalization occurred only in the mesh arm (2/115; 2%). Visceral organ injury occurred in 3% to 5% per arm, and events that changed intraoperative management in 2% to 4%. Modified Dindo grade III or higher events and serious adverse events did not differ among arms, and new or worsening dyspareunia occurred in 9% to 11% per arm. Eight participants died during follow-up (two native tissue, one sacrocolpopexy, five mesh); one death from cardiorespiratory arrest on postoperative day 16 was judged possibly related to the intervention.[1]
Limitations
The composite treats any failure as permanent and includes a symptom of any bother, which may contribute to failure rates of 28% to 43% alongside the high satisfaction and global improvement reported in every arm. The mesh arm was truncated by the 2019 FDA action (five participants re-randomized), the number of failures in the mesh and sacrocolpopexy arms was small, and the alpha was divided across comparisons; the mesh-versus-native-tissue result is therefore sensitive to the analysis population. The Uphold LITE kit is no longer marketed in the United States.[1]
Pandemic restrictions made physical examination unavailable at 294/670 visits (44%) in 2020 and 181/622 (29%) in 2021, leaving the assessment of time to failure incomplete at more than 30% of visits in months 30 to 54; 301/360 participants (84%) had a final-visit examination, and 296 (82%) completed the study. The native-tissue arm combined two operations, 83.9% of participants were White, and trainees took part in the operations.[1]
In conversation
- Conflicts with VUE (2020). Same vault question; ASPIRe's 36-month composite failure favored sacrocolpopexy, while VUE's 12-month symptom score did not differ.
- Parallel to OPTIMAL (2014). ASPIRe's native-tissue arm allowed the two operations OPTIMAL compared: sacrospinous fixation (82% of the arm) or uterosacral suspension.
- Parallel to SUPeR (2019). Also tested the Uphold mesh kit, with hysteropexy; ASPIRe cites its mesh-exposure rates for comparison.
- Parallel to SUPeR (2019). Same Pelvic Floor Disorders Network and composite failure definition; ASPIRe enrolled women with vault prolapse after hysterectomy.
ASPIRe's native-tissue arm allowed either sacrospinous fixation or uterosacral suspension, the two vaginal operations OPTIMAL randomized against each other. SUPeR also used the Uphold device, with hysteropexy, and reported a vaginal mesh exposure rate of 8% that fell to 3% over time with no reoperation; ASPIRe found exposure in 3% to 5%, with dyspareunia and vaginal shortening below the rates reported for earlier-generation kits. A July 2023 Cochrane review found prolapse awareness, prolapse on examination and reoperation more frequent after transvaginal procedures than after sacrocolpopexy; ASPIRe found no difference in postoperative prolapse symptoms among arms and a lower reoperation rate than that review reported, with no difference between arms.[1]
Report history
| Published | Report | Cutoff | Headline results | Citation |
|---|---|---|---|---|
| 2024-05-22 | 36-month randomized report · primary | — | Adjusted 36-month failure probability, sacrocolpopexy versus native-tissue repair (superiority, alpha 0.01, MITT-NTR population): 28% vs 43%; HR 0.57; 99% 0.33–0.98; P 0.008 Met Adjusted 36-month failure probability, transvaginal mesh versus sacrocolpopexy (noninferiority, margin HR 1.93, alpha 0.03, per-protocol population): 26% vs 27%; HR 1.05; P 0.01 Met Adjusted 36-month failure probability, transvaginal mesh versus native-tissue repair (superiority, alpha 0.01, MITT-NTR population): 29% vs 43%; HR 0.6; 99% 0.34–1.03; P 0.02 Not met Step-down superiority test, transvaginal mesh versus sacrocolpopexy (alpha 0.03, modified intention-to-treat): 27% vs 29%; HR 1.08; 97% 0.65–1.78; P 0.76 Not met Supportive per-protocol analysis, transvaginal mesh versus native-tissue repair: Mesh met the superiority threshold in this supportive population only; the primary population did not.; HR 0.57; 99% 0.32–1; P 0.01 Crude cumulative failure, modified intention-to-treat: 32% (38/119) vs 32% (37/116) vs 45% (55/123); — Descriptive Retreatment (pessary or surgery) through 36 months: 4% (5/120) vs 3% (3/113) vs 7% (8/118); P 0.33 Much better or very much better at 3 years: 95% (88/93) vs 94% (84/89) vs 87% (79/91); P 0.12 Mean postoperative leading edge of prolapse through 36 months, cm: -1.4 cm vs -0.9 cm vs -0.6 cm; — | Menefee SA, Richter HE, Myers D, et al. Apical suspension repair for vaginal vault prolapse: a randomized clinical trial. *JAMA Surg.* 2024;159(8):845-855. doi:10.1001/jamasurg.2024.1206 DOI |
| 2025-02-06 | Body image and sexual function · secondary | — | Change in Body Image in Pelvic Organ Prolapse (BIPOP) score from baseline, 335 women: 123 native tissue, 107 sacrocolpopexy and 105 mesh. Improved by 6 months and stayed improved to 36 months in every arm, with no difference among arms in the change or in the proportion reaching the minimally important difference.; — Sexual activity across visits and association of BIPOP change with PISQ-IR change: 99/335 (30%) were sexually active at every visit and 131/335 (39%) at none. Among sexually active women, BIPOP and PISQ-IR changes were correlated at each visit, and the association persisted after adjustment for baseline sexual function, site, age, surgical arm and baseline dyspareunia.; P <0.001 | Andy UU, Nowak K, Menefee SA, et al. Body image and sexual function improve following prolapse repair. *Am J Obstet Gynecol.* 2025;233(3):182.e1-182.e12. doi:10.1016/j.ajog.2025.01.042 DOI |
| 2025-11-08 | Frailty and mobility in women aged 65 or older · secondary | — | Prefrail or frail (Robinson Frailty Index 2 or higher) versus nonfrail, adjusted hazard ratio: Nested cohort of 146 women aged 65 or older (50 native tissue, 47 sacrocolpopexy, 48 mesh). Compromised mobility was also associated with shorter time to failure.; HR 2.1; 95% 1.2–3.6 Prefrail or frail women living alone before surgery versus nonfrail women, changes in living arrangements for extra support immediately after surgery: 19% versus 6%. Other geriatric-specific outcomes did not differ between prefrail or frail and nonfrail women.; P 0.04 | Erekson E, Menefee SA, Whitworth R, et al. Outcomes by frailty and mobility in older patients undergoing major urogynecologic surgery: a planned supplementary study of the apical suspension repair for vault prolapse in a three-arm randomized (ASPIRe) trial. *Am J Obstet Gynecol.* 2026;234(3):689-729. doi:10.1016/j.ajog.2025.11.002 DOI |
References
1. Menefee SA, Richter HE, Myers D, et al. "Apical Suspension Repair for Vaginal Vault Prolapse: A Randomized Clinical Trial." JAMA Surg. 2024;159(8):845-855. doi:10.1001/jamasurg.2024.1206
2. Andy UU, Nowak K, Menefee SA, et al. "Body image and sexual function improve following prolapse repair." Am J Obstet Gynecol. 2025;233(3):182.e1-182.e12. doi:10.1016/j.ajog.2025.01.042
3. Erekson E, Menefee SA, Whitworth R, et al. "Outcomes by frailty and mobility in older patients undergoing major urogynecologic surgery: a planned supplementary study of the apical suspension repair for vault prolapse in a three-arm randomized (ASPIRe) trial." Am J Obstet Gynecol. 2026;234(3):689-729. doi:10.1016/j.ajog.2025.11.002