Sociedad Americana de Hirudoterapia

Randomised controlled trial with medical leeches for osteoarthritis of the knee

Stange R, Moser C, Hopfenmueller W, Mansmann U, Buehring M, Uehleke B (2012) · Complementary Therapies in Medicine · n=52

RCT evidence detailTrial reference
GRADE LowCohort / case seriesCondition: Knee Osteoarthritis
Sample size of this trial compared with other Knee Osteoarthritis trialsWang H 2018264Lauche R 2025240Lauche R 2014237Farzali S 2025181Cui Y 2024144Andereya S 2008113Andereya S 2008113Sarbaev IS 201996Isik M 201790Stange R 201252
This trial (highlighted) by sample size alongside other indexed Knee Osteoarthritis trials. Larger trials generally carry more statistical weight.

Study Profile

Design
single-center, unblinded, randomised controlled trial with crossover design at day 42 (Charité-Universitätsmedizin Berlin-Campus Benjamin Franklin, Department for Natural Medicine)
Sample size (n)
52
Intervention
Single application of 8 Hirudo medicinalis leeches periarticularly around the symptomatic knee (group 1, n=27)
Comparator
Transcutaneous electrical nerve stimulation (TENS) (group 2, n=25); cross-over at day 42 with further observation through day 63
Primary endpoint
Change in Lequesne's combined index for pain and function (L.I.) and overall assessment of complaints by visual analogue scale (VAS) between days 0 and 21
Primary result
Lequesne's index improved from 12.07 to 9.37 in leech group and VAS from 5.89 to 4.16 cm (p<0.001) with no significant change in TENS arm; effect size as group difference -2.50 for L.I. (95% CI -3.88 to -1.11) and -1.86 cm for VAS (95% CI -2.85 to -0.87)
Follow-up duration
63 days

Key Findings

  • Independent Berlin Charité replication of the Essen-group leech-knee-OA signal in an unblinded crossover RCT
  • Lequesne's index improved by 2.7 points within 21 days of a single 8-leech session (p<0.001)
  • VAS pain dropped 1.73 cm in leech arm vs no significant change in TENS comparator over 21 days
  • Crossover at day 42 introduced phase effects that limited confirmatory between-group analysis to first period
  • 12 patients (23%) did not complete the trial, mostly due to non-compliance; no serious adverse events reported

Limitations

  • Unblinded design - both patients and outcome assessors aware of allocation
  • Crossover with phase effects forced restriction of confirmatory analysis to first period only
  • Single-center, single-country (Berlin Charité) - generalizability untested
  • High dropout rate (23%) raises risk of attrition bias
  • TENS comparator parameters and adherence not fully described

Clinical Implications

Stange 2011/2012 is the second independent German RCT of leech therapy for knee OA, conducted at Berlin Charité rather than at the Essen group that produced Michalsen 2003 and Andereya 2008. Its main contribution is the use of an active non-pharmacologic comparator (TENS) rather than topical diclofenac, and its addition to the GRADE evidence pool that supports leech therapy as a non-NSAID option. The crossover design and high dropout rate weaken individual-trial certainty, but the consistent direction of effect across three independent German centers strengthens the cumulative case for moderate-quality evidence in symptomatic knee OA management.

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