An open label,randomized clinical trial to compare the tolerability and efficacy of ivermectin plus diethylcarbamazine and albendazole vs. diethylcarbamazine plus albendazole for treatment of brugian filariasis in Indonesia

Improved treatments for lymphatic filariasis (LF) could accelerate the global elimination program for this disease. A triple drug combination of the anti-filarial drugs ivermectin, diethylcarbamazine (DEC) and albendazole (IDA) has been shown to be safe and effective for achieving sustained clearance of microfilariae (Mf) of the filarial parasite Wuchereria bancrofti from human blood. However, the triple drug combination has not been previously been evaluated for treatment of brugian filariasis, which accounts for about 10% of the global LF burden. This hospital-based clinical trial compared the safety and efficacy of IDA with that of the standard treatment (DEC plus albendazole, DA) in persons with Brugia timori infections on Sumba island, Indonesia. Fifty-five asymptomatic persons with B. timori Mf were treated with either a single oral dose of IDA (28 subjects) or with DEC plus albendazole (DA, 27 subjects). Participants were actively monitored for adverse events (AE) for two days after treatment by nurses and physicians who were masked regarding treatment assignments. Passive monitoring was performed by clinical teams that visited participant’s home villages for an additional five days. Microfilaremia was assessed by membrane filtration of 1 ml night blood at baseline, at 24h and one year after treatment. IDA was more effective than DA for completely clearing Mf at 24 hours (25/28, 89% vs. 8/27, 30%, P < 0.001). By 12 months after treatment, only one of 27 IDA recipients had Mf in their blood (4%) vs. 10 of 25 (40%) in persons treated with DA (P = 0.002). Approximately 90% of participants had antibodies to recombinant filarial antigen BmR1 at baseline. Antibody prevalence decreased to approximately 30% in both treatment groups at 12 months. About 45% of persons in both treatment groups experienced AE such as fever, muscle aches, lower back, joint and abdominal pain. These were mostly mild and most common during the first two days after treatment. No participant experienced a severe or serious AE. This study showed that IDA was well-tolerated and significantly more effective for clearing B. timori Mf from the blood than DA. Larger studies should be performed to further assess the safety and efficacy of IDA as a mass drug administration regimen to eliminate brugian filariasis.Trial Registration: {"type":"clinical-trial","attrs":{"text":"NCT02899936","term_id":"NCT02899936"}}NCT02899936.     

Tissue post-classification using the measured acoustic signals during 355 nm laser atherectomy procedures

The current laser atherectomy technologies to treat patients with challenging (to-cross) total chronic occlusions with a step-by-step (SBS) approach (without leading guide wire), are lacking real-time signal monitoring of the ablated tissues, and carry the risk for vessel perforation. We present first time post-classification of ablated tissues using acoustic signals recorded by a microphone placed nearby during five atherectomy procedures using 355 nm solid-state Auryon laser device performed with an SBS approach, some with highly severe calcification. Using our machine-learning algorithm, the classification results of these ablation signals recordings from five patients showed 93.7% classification accuracy with arterial vs nonarterial wall material. While still very preliminary and requiring a larger study and thereafter as commercial device, the results of these first acoustic post-classification in SBS cases are very promising. This study implies, as a general statement, that online recording of the acoustic signals using a noncontact microphone, may potentially serve for an online classification of the ablated tissue in SBS cases. This technology could be used to confirm correct positioning in the vasculature, and by this, to potentially further reduce the risk of perforation using 355 nm laser atherectomy in such procedures.