Patient‑reported health outcomes for severe knee osteoarthritis after conservative treatment with an intra‑articular cell‑free formulation for articular cartilage regeneration combined with usual medical care vs. usual medical care alone: A randomized controlled trial

Abstract

Osteoarthritis (OA) is a major public health problem characterized by joint pain, fatigue, functional limitation and decreased quality of life of the patient, which results in increased use of healthcare services and high economical costs. A promising novel bioactive cell-free formulation (BIOF2) for cartilage regeneration has recently been tested in pre-clinical and clinical trials, and has demonstrated a success rate similar to that of total joint arthroplasty for the treatment of severe knee OA. The present study evaluated the efficacy of treatment with BIOF2, by including it within a conservative regimen of ‘usual medical care’ of knee OA, and whether its efficacy was affected in subgroups of patients presenting with comorbidities that exacerbate OA. A prospective, randomized, 2-arm parallel group phase III clinical trial was conducted, which included 105 patients in the ‘usual medical care’ group (paracetamol/NSAIDs and general care provided by the family physician) and 107 patients in the BIOF2 group (usual medical care + intra-articular BIOF2 application at 0, 1 and 2 months). Two aspects were evaluated at 0, 6 and 12 months: i) Minimal clinically important improvement (MCII), based on 30% improvement of pain from the baseline; and ii) the Patient Acceptable Symptom State (PASS), a questionnaire that determines patient well-being thresholds for articular pain and function. Adverse effects and regular NSAID use were registered. At 12 months, BIOF-2 treatment produced MCII in 70% of the patients and >50% achieved PASS. Excluding the patients with class 2 obesity or malalignment conditions ( genu varum or genu valgum >20 degrees), the experimental treatment produced MCII and PASS in 100 and 92% of patients, respectively, compared with 25 and 8% in the group of usual medical care (P<0.001). No patient with malalignment and treatment with BIOF2 achieved PASS. Notably, there were no serious adverse effects. To conclude, BIOF2 is a safe therapeutic alternative that is easy to implement together with usual medical care for knee OA. Trial registration: Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000277. Retrospectively registered June, 2018.

Patient-Reported Health Outcomes After Treatment of COVID-19 with Nebulized and/or Intravenous Neutral Electrolyzed Saline Combined with Usual Medical Care Versus Usual Medical care alone: A Randomized, Open-Label, Controlled Trial.

“…The second primary end point was the Patient Acceptable Symptom State (PASS), defined as the value of symptoms the patient considered to be well-being thresholds of pain and function. Our study incorporated the most widely used anchoring question to identify PASS cut-off points, which was: “Taking into account all your daily activities, do you consider your current state satisfactory in relation to pain level and functional impairment?” The response options were “Yes” or “No” [ 35 ][ 36 ](34)[ 37 ]. Treatment success was defined as no disease progression, or a PASS answered in the affirmative on days 3, 5, or 7 of follow-up.…”

“…The VAS was selected because it is the validated scale that best evaluates pain in diseases (28,29), at present, and because it has also been used as a primary endpoint in other clinical trials (30). Patients completed the previously validated fatigue VAS (0–10 scale) [ 37 ], which states: “How much of a problem has unusual fatigue or tiredness been for you today” and was anchored from 0 (fatigue is not a problem) to 10 (fatigue is a major problem). Daily coughing episodes were reported by the patient on a numerical scale from 0 to 20.…”

“…Our study incorporated the most widely used anchoring question to identify PASS cut-off points, which was: "Taking into account all your daily activities, do you consider your current state satisfactory in relation to pain level and functional impairment?" The response options were "Yes" or "No" [35][36](34) [37]. Treatment success was de ned as no disease progression, or a PASS answered in the a rmative on days 3, 5, or 7 of follow-up.…”

“…The response options were measured on the 0-10 VAS, from 'very well' (score of 0) to 'very poorly' (score of 10). That question is validated in the Routine Assessment of Patient Index Data 3 (RAPID3), which is a pooled index of the three patient-reported Core Data Set measures of the American College of Rheumatology, and it has previously been used to determine the activity of autoimmune diseases, degenerative diseases, such as osteoarthritis (18), and infectious diseases with a strong component of general malaise, such as chikungunya fever (37). That end point is similar to the symptom severity score (self-assessed using a 10-point VAS) recently used in a clinical trial that evaluated the e cacy of hydroxychloroquine in non-hospitalized patients with COVID-19 [38].…”

“…If there were more than 20 episodes, they were registered as 20. Dyspnea was determined once a day through the Borg scale, from 0 to 10, in which 0 is no dyspnea and 10 is extremely severe dyspnea [37]. Nausea, vomiting, diarrhea, dizziness, conjunctivitis, rhinorrhea, exanthema, skin rash, and loss of sense of smell or taste were catalogued as present or absent for each day of follow-up.…”