Table 4: Summary of included bulking agent trials.

StudyNAge, yTreatmentStudy designStudy durationEfficacy measuresEfficacy outcomes

Glutaraldehyde cross-linked (GAX) collagen

Bent et al. 2001 [50]90Mean, 60.9
Range, 35–86
Up to 3 injections, as needed, over 6 mosOpen label, single arm12 mosContinence grade; diaries; LPP testing, QOL questionnaireDry: 21%
Improved: 21%
Improved LPP: 54%
QOL improvement: 62%
≥1 continence grade improvement: 21%

Corcos and Fournier 1999 [19]40Mean, 2.3
Range, 38–82
Up to 5 injections, as neededOpen label, single armMean follow-up, 50 mosDirect patient questioning; PVR test; stress pad weight test; Valsalva LPPCured: 30%
Improved: 40%
All cured patients had PVR <10 mL and negative pad tests

Elsergany et al. 1998 [43]33Mean, 64
Range, 19–97
Up to 3 injections, as neededOpen label, single armMean follow-up, 18.8 mosStamey Urinary Incontinence Scale; daily pad usage; diariesCured: 48.5%
≥1 Stamey Scale grade improvement: 33.3%
Improved from baseline, all 𝑃 < . 0 5

Herschorn et al. 1996 [44]187Mean, 62.9
Range, 15–94
Up to 3 injectionsOpen label, single armMean follow-up, 22 mosDirect patient questioningCured: 23%
Improved: 52%

Homma et al. 1996 [45]78Mean, 57.1–63.5Injections as neededOpen label, single arm24 mosPatient-administered questionnaireNo SUI leaks: 6.7%
SUI episodes daily: 50%
<1 SUI episode/wk: 16.7%
<1 SUI episode/day: 26.7%
Mean injections, 1.9

Monga et al. 1995 [53]60Mean, 64
Range, 20–90
Up to 3 injectionsOpen label, single arm24 mosDirect patient questioning; cystometry; stress pad weight testPatient-rated cured at 3, 12, 24 mos: 46%, 40%, 48%; improved: 40%, 37%, 20%
Objective measures (cystometry/pad weight), cured at 3, 12, 24 mos: 61%, 54%, 48%
Mean injections: 1.6

Richardson et al. 1995 [46]42Mean, 64
Range, 28–88
1–8 injections, as neededOpen label, single armMean follow-up, 46 mosLPP testing; incontinence grades (0–3)Cured: 40%
Greatly improved/improved: 43%
Unchanged/worse: 17%
LPP improvement in women cured/greatly improved: 65.4 cmH2O
Mean injections: 2.4 in those cured/greatly improved; 4.1 in those improved/unchanged/worse

Smith et al. 1997 [47]9467Injections as neededOpen label, single arm≥18 mosPatient self-reportInitially dry/improved: 67%
Of these, 66.7% still dry/improved at 18 mos; most continent with 1–3 injections, 7 required 4 or more

Winters et al. 2000 [48]58Mean, 73.2
Range, 65–86
Injections as neededOpen label, single arm24 mosTelephone interviewMaximal/moderate improvement: 62.5%
Maximal/moderate QOL improvement: 45.0%
Mean injections: 1.9
Mean time to SUI recurrence: 7.9 months

Carbon-coated zirconium beads

Chrouser et al. 2004 [51]86Mean, 67Carbon-coated zirconium beads ( 𝑛 = 4 3 )
GAX collagen ( 𝑛 = 4 3 )
Injections as needed
Post hoc, open label versus GAX collagen (control)36 mosPatient questionnaireSUI improvement at 12, 24, 26 mos:
Zirconium beads: 35%, 33%, 21%
GAX collagen: 33%, 19%, 9%
Overall, 𝑃 = N S
Mean injections: N/A

Lightner et al. 2001 [52]235Mean, 57.7
Mean, 57.0
Range, 26–84
Carbon-coated zirconium beads ( 𝑛 = 1 1 5 )
GAX collagen ( 𝑛 = 1 2 0 )
Maximum 5 injections, as needed
Randomized, controlled, single blind versus GAX collagen (control)12 mosStamey Urinary Incontinence Scale; stress pad weight test≥1 Stamey Scale grade improvement:
Zirconium beads: 66.1%
GAX collagen: 65.8%
𝑃 = N S
Mean change in pad weight:
Zirconium beads: 27.9 g
GAX collagen: 26.4
𝑃 = N S
Mean injections: 1.69 versus 1.55

Polydimethylsiloxane

Ghoniem et al. 2009 [54]247Mean, 61Polydimethylsiloxane ( 𝑛 = 1 2 2 )
GAX collagen ( 𝑛 = 1 2 5 )
Injections as needed
Randomized, single blind versus GAX collagen12 mosStamey Urinary Incontinence Scale; stress pad weight test; I-QOL scores≥1 Stamey Scale grade improvement: Polydimethylsiloxane: 61.5%
GAX collagen: 48.0%
I-QOL improvement:
Polydimethylsiloxane: 28.7%
GAX collagen: 26.4%
Pad weight test, 𝑃 = N S

Koelbl et al. 1998 [55]32Mean, 64.3
Range, 39–85
Up to 2 injectionsOpen label, single arm12 mosStamey Urinary Incontinence Scale; cough stress test; urethral pressure measurementsCured: 60%
Increased maximal urethral pressure, 𝑃 = . 0 3

Maher et al. 2005 [56]45Mean, 65 Range, 34–84
Mean, 63 Range, 43–81
Polydimethylsiloxane ( 𝑛 = 2 3 )
Pubovaginal sling ( 𝑛 = 2 2 )
Randomized, controlled60 monthsPatient questionnaireResponse rate, 60% in both groups
Cured/improved:
Injection: 21%
Sling: 69%

Radley et al. 2001 [57]56Mean, 53
Range, 26–81
Up to 3 injectionsOpen label, single armMean follow-up, 19 monthsPatient questionnaireCured/improved: 19.6%
Improved: 39.3%
No longer using pads: 19.6%

Tamanini et al. 2003 [58]21Median, 47.4
Range, 33–54
Injections as neededOpen-label, single arm, interim results12 mosStamey Urinary Incontinence Scale; King’s Health Questionnaire; pad usage; LPP testing; stress pad weight testCured: 76.2%
Improved: 66.7%
Mean decrease in daily pad usage: 3.1
Mean pad weight decrease: 45.7 g

Tamanini et al. 2006 [59]21aMedian, 47.4
Range, 33–54
Injections as neededOpen label, single arm60 mosStamey Urinary Incontinence Scale; King’s Health Questionnaire; pad usage; LPP testing; stress pad weight testCured: 40.0%
Improved: 33.3%
Mean decrease in daily pad usage: 2.6
Mean pad weight decrease: 47.9 g
ter Meulen et al. 2009 [60]45Mean, 55
Range, 40–76
Up to 2 injections, as needed ( 𝑛 = 2 4 )
At-home PFMT ( 𝑛 = 2 1 )
Randomized, controlled, open label versus PFMT (control)12 mosI-QOL scores; patient questionnaire; stress pad weight testPolydimethylsiloxane:
Cured: 88.9%
Improved: 82.4%
PFMT: 12-mo results N/A

Zullo et al. 2005 [61]61Mean, 69.7
Range, 55–82
One-time injectionObservational, open-label, single arm60 mosVAS scores; diaries, cough stress test; PVR; LPPCured: 18%
Improved: 39%
Cough stress test:
Cured patients: negative
Improved patients: positive only when standing
Mean decrease in daily SUI episodes: 3.8
Mean changes in PVR and LPP: 𝑃 = N S versus baseline

Calcium Hydroxylapatite

Mayer et al. 2007 [62]296Mean, 61Up to 5 injections, as neededRandomized, single blind versus GAX collagen12 mosStamey Urinary Incontinence Scale≥1 Stamey Scale grade improvement: 63.4% (calcium Hydroxylapatite) versus 57.0% (GAX collagen); 𝑃 = . 3 4

Abbreviations: LPP, leak point pressure; N/A, not available; NS, not significant; PVR, postvoid residual; SUI, stress urinary incontinence; QOL, quality of life; VAS, visual analogue scale.
aThese patients were already counted in Tamanini et al. 2003 [58], thus they were not included in the total patient numbers as given in the text.