Two peer-reviewed cohort studies have followed patients after a single injection of Crespine Gel or Crespine Gel+. Both are open-label and single-arm — there is no placebo or active control — and both report sustained improvements in pain and function. We summarise them here with their numbers and their limitations.
Crespine Gel
Single injection of Crespine Gel in knee osteoarthritis — nine-month post-marketing study
Design
Prospective, open-label, single-arm phase IV study; four centres in Jordan; registered with the Jordanian FDA (MDV-JO-201/01)
Patients
109 enrolled, 84 analysed; age 55.8 ± 9.3 years; 64 % men; BMI 30.5; Kellgren–Lawrence grade II 35 %, grade III 56 %
Intervention
One intra-articular injection of 2 ml Crespine Gel
Follow-up
9 months; visits at months 3, 6 and 9, telephone contact in between
Outcome measure
WOMAC Likert 3.0 (pain 0–20, stiffness 0–8, function 0–68)
WOMAC scores (mean)
WOMAC scores (mean)
Measure
Baseline
Month 3
Month 6
Month 9
Pain (0–20)
10.99
3.12
2.87
3.36
Stiffness (0–8)
3.77
0.44
0.45
0.42
Function (0–68)
34.35
11.99
10.49
11.49
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All changes versus baseline p < 0.0001. OMERACT-OARSI pain responders at the 50 % threshold: 69 of 84 patients (82 %).
Safety
33 of 84 patients (39 %) reported increased knee pain within 72 hours of the injection, in some cases with redness or swelling; symptoms resolved within two to three days with standard analgesics. No serious adverse events were reported.
Limitations
No control group, no blinding, no a-priori sample-size calculation; 23 % of enrolled patients were excluded from the analysis because of missing visits. Funded by BioPolymer GmbH & Co. KG.
Bashaireh K, Naser Z, Hawadya KA, Sorour S, Al-Khateeb RN. Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing Phase IV study. Drug Des Devel Ther. 2015;9:2063–2072. doi:10.2147/DDDT.S81524 Source
Crespine Gel+
Single injection of Crespine Gel+ in knee osteoarthritis — twelve-month prospective study
Design
Prospective, single-arm, open-label observational cohort; single centre (Sultan Abdul Halim Hospital, Malaysia); June 2023 – June 2025; a-priori sample size 109
Patients
111 enrolled, 92 (83 %) completed twelve months; age 65.1 ± 7.8 years; 67 % women; BMI 28.2; Kellgren–Lawrence grade II 40 %, grade III 51 %
Intervention
One intra-articular injection of 2 ml Crespine Gel+, superolateral approach
Follow-up
3 and 12 months
Outcome measures
KOOS4 (primary), VAS pain 0–10, KOOS subscales; linear mixed models adjusted for age, sex, BMI and Kellgren–Lawrence grade
Adjusted means
Adjusted means
Measure
Baseline
Month 3
Month 12
Change at 12 months (95 % CI)
KOOS4 (0–100)
62.2
70.8
71.0
+8.8 (5.5 to 12.1)
VAS pain (0–10)
4.80
3.12
3.17
−1.6 (−2.0 to −1.3)
KOOS ADL
63.3
74.2
74.2
+10.2 (6.4 to 13.9)
KOOS quality of life
45.7
52.0
56.4
+10.6 (6.4 to 14.9)
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All changes versus baseline p < 0.001; no significant change between month 3 and month 12. Use of tramadol, celecoxib, topical analgesics and physiotherapy decreased among completers.
Safety
Two of 111 patients (1.8 %) reported transient injection-site pain that resolved within 48 hours. No septic arthritis, hypersensitivity reaction or systemic complication occurred.
Limitations
No control group, no blinding, single centre; 17 % attrition without sensitivity analysis; patient-reported outcomes only. Partial financial support from Nexgen Medical Sdn. Bhd., Malaysia.
Suppan VKL, Tew MM, Muthusamy H, Voon JM, Ramli NAMN, Phuah ASJ, Murugaiah D. Long-term functional and clinical outcomes of intraarticular double-cross-linked high molecular weight hyaluronic acid (Crespine Gel Plus) injection in knee osteoarthritis: a one year prospective study. BMC Musculoskelet Disord. 2026;27:209. doi:10.1186/s12891-026-09588-1 Source
Mentioned in reviews
Vincent P. Intra-articular hyaluronic acid in the symptomatic treatment of knee osteoarthritis: a meta-analysis of single-injection products. Curr Ther Res Clin Exp. 2019;90:39–51 — includes the 2015 Crespine Gel study among 28 single-injection studies. Source
Pojala CV et al. The potential of intra-articular therapies in managing knee osteoarthritis: a systematic review. Clin Pract. 2024;14(5):1970–1996 — tabulates the 2015 Crespine Gel study. Source
No randomised controlled trial and no head-to-head comparison with other viscosupplements has been published for Crespine Gel or Crespine Gel+. Data on hip osteoarthritis are limited to clinical experience. We will update this page as new data are published.
