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An intra-articular injection of LMW human serum albumin is safe and effective for knee OA
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June 2014
An intra-articular injection of LMW human serum albumin is safe and effective for knee OA
Study Type:Therapy
OE Level Evidence:1
Journal Level of Evidence:N/A
A randomized clinical trial to evaluate two doses of an intra-articular injection of LMWF-5A in adults with pain due to osteoarthritis of the knee
PLoS One. 2014 Feb 3;9(2):e87910. doi: 10.1371/journal.pone.0087910. eCollection 2014.Did you know you're eligible to earn 0.5 CME credits for reading this report? Click Here
Synopsis
329 patients with symptomatic knee osteoarthritis (OA) were randomized to receive either Low Molecular Weight Fraction of 5% human serum albumin (LMWF-5A) or saline vehicle solution, each at a dose of either 4 or 10 mL. The purpose of this study was to determine the analgesic efficacy and safety of LMWF-5A in this study population. Results indicated that both the 4-mL and 10-mL volumes of the LMWF-5A solution were safe and yielded significantly better pain scores, functional outcome, and overall assessment of disease severity, when compared to a saline vehicle solution. These effects were especially pronounced in patients with severe OA, and those who received a prior knee injection.
The data from this ACE report was included in the analysis for OE Recommends - Knee Osteoarthritis. Click here to learn more
Publication Funding Details
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Funding:
Industry funded
Sponsor:
Ampio Pharmaceuticals, Inc.
Conflicts:
Company Employee
Was the allocation sequence adequately generated?
Was allocation adequately concealed?
Blinding Treatment Providers: Was knowledge of the allocated interventions adequately prevented?
Blinding Outcome Assessors: Was knowledge of the allocated interventions adequately prevented?
Blinding Patients: Was knowledge of the allocated interventions adequately prevented?
Was loss to follow-up (missing outcome data) infrequent?
Are reports of the study free of suggestion of selective outcome reporting?
Were outcomes objective, patient-important and assessed in a manner to limit bias (ie. duplicate assessors, Independent assessors)?
Was the sample size sufficiently large to assure a balance of prognosis and sufficiently large number of outcome events?
Was investigator expertise/experience with both treatment and control techniques likely the same (ie.were criteria for surgeon participation/expertise provided)?
Yes = 1
Uncertain = 0.5
Not Relevant = 0
No = 0
The Reporting Criteria Assessment evaluates the transparency with which authors report the methodological and trial characteristics of the trial within the publication. The assessment is divided into five categories which are presented below.
4/4
Randomization
3/4
Outcome Measurements
4/4
Inclusion / Exclusion
4/4
Therapy Description
4/4
Statistics
Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA. J Clin Epidemiol. 1992;45:255-65
The Fragility Index is a tool that aids in the interpretation of significant findings, providing a measure of strength for a result. The Fragility Index represents the number of consecutive events that need to be added to a dichotomous outcome to make the finding no longer significant. A small number represents a weaker finding and a large number represents a stronger finding.
Why was this study needed now?
The prevalence of knee osteoarthritis (OA) is on the rise. This increase - potentially attributable (in part) to the increasing rates of obesity within the population - in concerning, as knee OA can significantly impact a patient's quality of life. Currently, conservative treatment for this inflammatory condition may include intra-articular corticosteroid or hyaluronan injections, or non-steroidal anti-inflammatory drugs (NSAIDs); however, these approaches are not supported by high-quality evidence. As a result, human serum albumin (HSA) has been proposed as an alternative in the management of knee OA. This study was needed to establish the analgesic efficacy and safety of the Low Molecular Weight Fraction of 5% HSA (LMWF-5A) for the treatment of patients with knee OA.
What was the principal research question?
Is the Low Molecular Weight Fraction of 5% human serum albumin (LMWF-5A) safe and effective for improving pain, stiffness, function and overall disease severity in patients with knee osteoarthritis?
Study Characteristics
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Population:
329 fully ambulatory patients (40-85 years of age) with symptomatic knee osteoarthritis (OA) radiologically confirmed within 6 months of screening. Included patients had moderate-severe pain in the affected knee. If patients presented with bilateral knee OA, then the knee that best satisfied treatment requirements was chosen for the study.
Intervention:
4 mL LMWF-5A group: Patients in this group (n=83; 3 discontinued by week 12) received a single, 4-mL intra-articular injection of the Low Molecular Weight Fraction of 5% human serum albumin (LMWF-5A). The HSA used in this study (OctaPharma, Lachen, Switzerland) was centrifuged and subject to ultrafiltration. The ultrafiltrate contained aspartyl-alanyl diketopiperazine (50-200 uM), as well as the excipients (sodium caprylate and sodium acetyltryptophanate), and was transferred for aseptic filling. (Mean age: 62.7 [SD 9.3]; 67% female)
10 mL LMWF-5A group: Patients in this group (n=82; 1 discontinued by week 12) received a single, 10-mL intra-articular injection of the Low Molecular Weight Fraction of 5% human serum albumin (LMWF-5A). The HSA used in this study (OctaPharma, Lachen, Switzerland) was centrifuged and subject to ultrafiltration. The ultrafiltrate contained aspartyl-alanyl diketopiperazine (50-200 uM), as well as the excipients (sodium caprylate and sodium acetyltryptophanate), and was transferred for aseptic filling. (Mean age: 62.8 [SD 8.4]; 56% female)
Comparison:
4 mL saline vehicle control group: Patients in this group (n=83) received a single, 4-mL, intra-articular injection of a saline vehicle. (Mean age: 60.7 [SD 8.3]; 69% female)
10 mL saline vehicle control group: Patients in this group (n=81; 2 discontinued by week 12) received a single, 10-mL, intra-articular injection of a saline vehicle. (Mean age: 63.8 [SD 10.0]; 62% female)
Outcomes:
The primary outcome was pain on the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain subscale (measured on a 5-point Likert scale). Secondary outcomes included the incidence and severity of adverse events, stiffness (assessed on the WOMAC stiffness subscale), physical function (assessed on the WOMAC function subscale), pain at rest and with movement, Patient's Global Assessment (PGA) of disease severity, and use of rescue analgesia (acetaminophen).
Methods:
RCT; Multi-Centre (9 sites); Double-blinded (patients & assessors)
Time:
Follow-up assessments were conducted by telephone at 2, 4, 8, and 10 weeks and in-clinic assessments took place at 6 and 12 weeks.
What were the important findings?
- In general, LMWF-5A improved pain significantly more (-0.93) compared to the control solution (-0.72) (estimated difference: -0.25; 95% CI -0.08 to -0.41; p=0.004). This significant between-group difference was apparent at week 4 (p=0.03), week 6 (p=0.04) and week 12 (p=0.004), but not at weeks 2 (p=0.14), 8 (p=0.06) or 10 (p=0.11).
- Over time ending at week 12, the percentage of pain score reduction was significantly greater when patients were administered LMWF-5A (42.3%) compared to the control solution (31.7%) (p<0.05).
- Compared to patients receiving the saline vehicle solution, those receiving LMWF-5A had significantly superior Patient's Global Assessment (PGA) of disease severity scores (-0.87 vs -0.65; p=0.01), physical function (-0.78 vs -0.64; p=0.04) and pain at rest (-0.91 vs -0.70; p=0.004).
- Whether patients were administered LMWF-5A or the saline vehicle solution, there was no significant difference in the number of acetaminophen pills consumed (median 24.0 vs 34.0; p=0.09), or stiffness (p>0.05).
- In patients with severe OA, LMWF-5A had a significant pain improvement compared to the saline solution (-0.42; 95% CI -0.08 to -0.77; p=0.02). Furthermore, patients who had previously received a knee injection had a significantly better mean pain outcome with LMWF-5A compared to control, whereas this finding was borderline-significant in patients who did not receive a previous injection.
- Between the LMWF-5A and control in injection groups, there were no significant differences in total adverse events (41% vs 47%), treatment-related adverse events (10% vs 13%), or serious adverse events (5% vs 6%). No serious adverse event was considered to be study-related and no deaths occurred.
What should I remember most?
In patients with knee osteoarthritis (OA), both the 4-mL and 10-mL volumes of the Low Molecular Weight Fraction of 5% human serum albumin (LMWF-5A) were safe and yielded significantly better pain scores, functional outcome, and overall assessment of disease severity, when compared to a saline vehicle solution. These effects were especially pronounced in patients with severe OA, and those who had received a prior knee injection. Stiffness and the amount of rescue analgesics consumed were not significantly different between groups.
How will this affect the care of my patients?
Results from this study support the administration of a single, intra-articular injection of Low Molecular Weight Fraction of 5% human serum albumin (LMWF-5A) in the treatment of knee osteoarthritis (OA). This finding is promising in patients with severe OA, for whom the only other treatment alternative may be surgical intervention. Additional long-term studies, with larger sample sizes, are needed to confirm these results.
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