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The article, 'double-blind, randomized controlled trial of therapeutic plasma exchanges vs sham exchanges in moderate-to- severe relapses of multiple sclerosis' (brochet 2019) describes a randomized controlled trial that compared therapeutic plasma exchange (tpe) with sham treatment in patients with steroid-resistant, moderate-to- severe multiple sclerosis relapse between 2011 and 2017.Patients had six tpe or six sham-tpe during the 2 weeks after inclusion on cobe spectra platform.Average patient age was 33.5 (range 18 to 65 years of age) majority female (71.5%) fourteen patients underwent tpe and seventeen underwent sham-tpe with either spectra optia or cobe spectra.1 patient developed a local hematoma in the tpe group.It is unknown at this time if medical intervention was required.Four patients in the sham-tpe group experienced adverse events (2 were hospitalized and 2 experienced ms relapses).It was unclear what proportion of these events occurred on cobe spectra/spectra optia.Specific details, such as patient information, was not included in the article, therefore this report is being provided as a summary of the events.The disposable set is not available for return because it was discarded by the customer.
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Investigation: there were no details regarding the adverse reactions that led to hospitalization for 2 patients or ms relapse for 2 patients.It was unknown if medical intervention was required for the one reported hematoma occurrence.There were also no details regarding the adverse reactions that led to hospitalization for 2 patients or ms relapse for 2 patients.Objective: to compare tpe to sham-tpe in patients with a recent steroid resistant moderate- to-severe ms relapse.Methods: patients presenting with an ms relapse of less than 2 months without improvement and 15 days after a course of steroids were randomized.Specific criteria were used for each relapse type to define moderate-to-severe disability.The primary endpoint was the proportion of patients with at least a moderate improvement based on objective and functional evaluation after 1 month.Patients and evaluating neurologists were blinded to group allocation.Because of the nature of the treatment, a special procedure was used for maintaining blinding.The physician of the apheresis center as well as the pharmacist at the center received the inclusion agreement and the allocated treatment arm by secured email from the randomization site.This physician of the exchange center administered the treatment according to this allocation without informing the patient or the investigating neurologist of the allocated treatment group.During the whole duration of the tpe or sham-tpe, the machine was masked by a folding screen before the patient was installed.All manipulations of the machine as well as the replacement of the products were performed without the patient's knowledge behind the shield and were similar between the two types of tpe to keep the patient from becoming aware of the treatment administered.Patients had six tpe or six sham-tpe during the 2 weeks after inclusion.Real tpe consisted of exchanging a defined volume of plasma (pv) with an equal volume of substitute product: 4% (20 g/500 ml) human albumin (vialebex, from laboratoire du fractionnement biologique [lfb]).Volume calculation was made using the apheresis device program based on patient's parameters, hematocrit, height, weight, and sex (1.0 pv exchange).The entry venous path route brought the patient's blood to the machine, which separated the blood elements from the plasma by centrifugation.The return venous path allowed the return of blood elements except for the plasma which was replaced by an equal volume of 4% albumin, a plasma replacement fluid used in apheresis.During this separation, citrate dextrose solution usp formula a (acd-a) was used as an anticoagulant with an anticoagulant-to-blood flow ratio between 1/10 and 1/12.To avoid side effects, 3 g calcium gluconate at 10% was used during this real tpe.Sham-tpe consisted of using the same technique as the actual tpe.The entry path brought the patient's blood to the machine, which separated the blood elements from the plasma by centrifugation.During this separation, acd-a was also used as an anticoagulant with an anticoagulant-to-blood flow ratio between 1/10 and 1/12.In contrast, the return path returned the blood including plasma elements to the patient without any substitution.During reinjection, the plasma was reintroduced with the anticoagulant citrate, a calcium chelating agent.To avoid side effects, calcium gluconate at 10% was used during this sham tpe.A dosage of 5 g was arbitrarily chosen to limit side-effects as much as possible.Table 1 summarizes the devices and procedures.The primary outcome was the proportion of patients with at least a moderate improvement based on objective and functional evaluation 1 month after the start of the treatment and detailed in data s1.In addition, the proportions of patients without improvement and the proportion of patients with weak, moderate, or full improvement based on a 5-grade scale were compared.The primary endpoint was calculated by the study statistician based on the neurologists' objective assessments and the patient's subjective functional assessment.The objective assessments were based on visual acuity, neurological examination, ambulation time or the nine-hole peg test according to the relapse type.Functional improvement was established by visual analogic scales (vas).This approach, adapted the methods used in the mayo clinic trial,19 allows to combine assessments of different type of clinical syndromes.Each syndrome was assessed by validated scales.This procedure is detailed in data s1.In addition, this primary endpoint was measured after 3 and 6 months.Secondary endpoints a significant difference was observed in favor of the tpe group for change of cfs score at months 1, 3, and 6 (table 5).Concerning edss change, a trend towards edss improvement in favor of the tpe group (p =.06) was observed at month 1, which was not confirmed at months 3 and 6.One serious adverse event (sae) was observed in the tpe group (local hematoma) but it was not classified as severe according to the common terminology criteria for adverse events.Four saes were observed in the sham group (two hospitalizations and two ms relapses).Results: thirty-eight patients were randomized.The intention-to-treat analysis included 14 patients in the tpe group and 17 in the sham-tpe group.The proportion of patients with at least moderate improvement at 1 month did not differ between the groups (p =.72), although 57.1% of the tpe group had full recovery compared with 17.6% of the sham group.Considering optic neuritis (on), a significant difference in the proportion of different levels of improvement was observed in favor of the tpe group (p =.04).The combined kurtzke's functional systems scores were significantly more improved in the tpe group than in the sham- tpe group at months 1 (p <.01), 3 (p <.05), and 6 (p <.05).No major side effects were observed.According to the journal article, consensus on the treatment of ms relapses is represented by high-dose corticosteroids, particularly high doses of intravenous (iv) methylprednisolone or oral methylprednisolone.According to therapeutic apheresis: a physician's handbook, adverse events occur during therapeutic procedures with a frequency of 4.8%.Some of the most common reactions include fever, urticaria, hypocalcemic symptoms, pruritus, dyspnea, tachycardia, and mild hypotension.Adverse effects related to vascular access are a frequent concern.Hematoma, venous sclerosis and thrombosis can complicate percutaneous needle puncture.Hemorrhage or pneumothorax or both may complicate cvc insertion, while thrombosis and infection are the most frequently observed complications of prolonged central venous access.The disposable sets were not available for return.Since this was a clinical study to compare tpe to sham-tpe in patients with a recent steroid resistant moderate-to-severe ms relapse between 2011 and 2017, the lot numbers are unknown.Since this was a clinical study to compare tpe to sham-tpe in patients with a recent steroid resistant moderate-to-severe ms relapse between 2011 and 2017, the lot numbers are unknown; therefore, a dhr search could not be conducted for the reported incident.All lots must meet acceptance criteria for release.Root cause: a definitive root cause for the patient hematoma could not be determined.Possible causes include but are not limited to: - poor phlebotomy technique causing the needle to unintentionally enter the tissue surrounding the blood vessel - dislodgement of the needle from the vein due to arm movement, a poorly secured needle, or an inadequate choice of venous site to puncture - an excessively high return flow rate - issues with the indwelling vascular access root cause for the reactions that led to hospitalization are unknown but may be due to the patient's underlying disease state or sensitivity to the procedure.Root cause for the ms relapses is related to the patient's underlying disease state.
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