Therapeutic ultrasound

CLOTBUST-HF: Hands-Free Ultrasound and tPA in Acute Stroke.

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Intracranial ultrasound treatment using an operator-independent device together with tissue plasminogen activator (tPA) in stroke patients appears to be safe and produced promising recanalization rates, a new study has shown.

The study, published online in Stroke on October 24, was led by Andrew D. Barreto, MD, University of Texas Health Science Center at Houston.

He explained to Medscape Medical News that ultrasound therapy causes the meshwork of fibrin strands within the clot to disperse, thereby allowing better access of tPA to the clot. “We are particularly targeting patients who have clots that are not likely to lyse completely with tPA — those with moderate to severe strokes,” Dr. Barreto noted.

“Many smaller studies have been performed with transcranial ultrasound and it does seem to have efficacy in helping to dissolve the clot,” he said. The most cited study is the original CLOTBUST(Combined Lysis of Thrombus in Brain Ischemia With Transcranial Ultrasound and Systemic TPA) study published in 2004 in the New England Journal of Medicine, which showed a recanalization rate of 38% with the combination of ultrasound and tPA vs 13% for those given tPA alone.

However, Dr. Barreto noted that delivery of ultrasound via cranial bone windows requires training for both anatomic localization and waveform recognition, which is considered impractical for large-scale use. “As you have to hold the ultrasound device at the same time as identifying the clot, it is too difficult to train enough people to perform the procedure as an emergency bedside therapeutic,” he said.

“Mass expansion of properly trained technicians or clinicians to provide 24/7 stroke coverage to complete a pivotal clinical trial of sonothrombolysis represents a major hurdle,” the researchers write in the Stroke paper.

http://img.medscape.com/news/2012/ht_120206_clot_bust_device_300x225.png

Operator-independent transcranial stroke treatment device.Source: The investigators

“To that end, the development of an operator-independent device that can target the proximal intracranial arteries without specialized neurovascular ultrasound training would make a large-scale, phase 3 clinical trial feasible,” they add.

Hands-Free Device

Such a “hands-free” device has now been manufactured by Cerevast Therapeutics, and the current study represents the first-ever exposure of patients with acute stroke to a combination of tPA and this hands-free ultrasound device. “This device has been manufactured so that it can be used without special training and be applied to all stroke patients by just placing it on their heads,” Dr. Barreto said.

“It is battery powered and easy to fit. One size fits all, with an adjustable head size and ear position,” he explained. “It has been designed so that the probes are positioned in the areas of thinnest bone of the skull: 6 probes on the left and 6 on the right. The device rotates and sequentially fires each probe, thus targeting all the areas of the brain where a large blood clot would be.”

For the current study, known as CLOTBUST-Hands Free (CLOTBUST-HF), 20 stroke patients with a median National Institutes of Health Stroke Scale score of 15 received standard-dose intravenous tPA, along with 2-MHz pulsed-wave ultrasound therapy delivered by the CLOTBUST-HF device used for 2 hours.

Sites of occlusion were middle cerebral artery in 14 patients, terminal internal carotid artery in 3 patients, and vertebral artery in 3 patients. All patients tolerated the entire 2 hours of ultrasound treatment, and none developed symptomatic intracerebral hemorrhage. No serious adverse events were related to the study device.

40% Recanalization Rate

At 2 hours, 40% of patients had complete recanalization and 10% had partial recanalization. Middle cerebral artery occlusions demonstrated the greatest complete recanalization rate at 57%. At 90 days, 5 patients (25%) had an excellent outcome, defined as a modified Rankin scale score of 0 to 1.

“The recanalization rate of 40% is in line with that shown in the NEJM paper. But we did not have a control group in this study,” Dr. Barreto commented. “At day 90 we had a lower percentage of patients with an excellent outcome than in the previous study, but we only had 20 patients so it is difficult to say much about a clinical outcome.”

“This is just a pilot study looking at safety of delivering ultrasound treatment to different areas of the brain. We didn’t see any safety issues and the results definitely suggest the approach is feasible,” he added.

A phase 3 trial — CLOTBUST-ER — is now underway with the hands-free device. The trial is being conducted in 830 patients from 14 countries, with results expected in 2 to 3 years.

CLOTBUST-HF: Hands-Free Ultrasound and tPA in Acute Stroke

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Intracranial ultrasound treatment using an operator-independent device together with tissue plasminogen activator (tPA) in stroke patients appears to be safe and produced promising recanalization rates, a new study has shown.

The study, published online in Stroke on October 24, was led by Andrew D. Barreto, MD, University of Texas Health Science Center at Houston.

He explained to Medscape Medical News that ultrasound therapy causes the meshwork of fibrin strands within the clot to disperse, thereby allowing better access of tPA to the clot. “We are particularly targeting patients who have clots that are not likely to lyse completely with tPA — those with moderate to severe strokes,” Dr. Barreto noted.

“Many smaller studies have been performed with transcranial ultrasound and it does seem to have efficacy in helping to dissolve the clot,” he said. The most cited study is the original CLOTBUST(Combined Lysis of Thrombus in Brain Ischemia With Transcranial Ultrasound and Systemic TPA) study published in 2004 in the New England Journal of Medicine, which showed a recanalization rate of 38% with the combination of ultrasound and tPA vs 13% for those given tPA alone.

However, Dr. Barreto noted that delivery of ultrasound via cranial bone windows requires training for both anatomic localization and waveform recognition, which is considered impractical for large-scale use. “As you have to hold the ultrasound device at the same time as identifying the clot, it is too difficult to train enough people to perform the procedure as an emergency bedside therapeutic,” he said.

“Mass expansion of properly trained technicians or clinicians to provide 24/7 stroke coverage to complete a pivotal clinical trial of sonothrombolysis represents a major hurdle,” the researchers write in the Stroke paper.
Operator-independent transcranial stroke treatment device.Source: The investigators

“To that end, the development of an operator-independent device that can target the proximal intracranial arteries without specialized neurovascular ultrasound training would make a large-scale, phase 3 clinical trial feasible,” they add.

Hands-Free Device

Such a “hands-free” device has now been manufactured by Cerevast Therapeutics, and the current study represents the first-ever exposure of patients with acute stroke to a combination of tPA and this hands-free ultrasound device. “This device has been manufactured so that it can be used without special training and be applied to all stroke patients by just placing it on their heads,” Dr. Barreto said.

“It is battery powered and easy to fit. One size fits all, with an adjustable head size and ear position,” he explained. “It has been designed so that the probes are positioned in the areas of thinnest bone of the skull: 6 probes on the left and 6 on the right. The device rotates and sequentially fires each probe, thus targeting all the areas of the brain where a large blood clot would be.”

For the current study, known as CLOTBUST-Hands Free (CLOTBUST-HF), 20 stroke patients with a median National Institutes of Health Stroke Scale score of 15 received standard-dose intravenous tPA, along with 2-MHz pulsed-wave ultrasound therapy delivered by the CLOTBUST-HF device used for 2 hours.

Sites of occlusion were middle cerebral artery in 14 patients, terminal internal carotid artery in 3 patients, and vertebral artery in 3 patients. All patients tolerated the entire 2 hours of ultrasound treatment, and none developed symptomatic intracerebral hemorrhage. No serious adverse events were related to the study device.

40% Recanalization Rate

At 2 hours, 40% of patients had complete recanalization and 10% had partial recanalization. Middle cerebral artery occlusions demonstrated the greatest complete recanalization rate at 57%. At 90 days, 5 patients (25%) had an excellent outcome, defined as a modified Rankin scale score of 0 to 1.

“The recanalization rate of 40% is in line with that shown in the NEJM paper. But we did not have a control group in this study,” Dr. Barreto commented. “At day 90 we had a lower percentage of patients with an excellent outcome than in the previous study, but we only had 20 patients so it is difficult to say much about a clinical outcome.”

“This is just a pilot study looking at safety of delivering ultrasound treatment to different areas of the brain. We didn’t see any safety issues and the results definitely suggest the approach is feasible,” he added.

A phase 3 trial — CLOTBUST-ER — is now underway with the hands-free device. The trial is being conducted in 830 patients from 14 countries, with results expected in 2 to 3 years.

This study was supported by the National Institute of Neurological Disorders and Stroke and the National Institutes of Health. Cerevast Therapeutics provided the study devices and was not involved in the study design, analysis, or manuscript preparation. A coauthor serves as a consultant to Cerevast Therapeutics Inc and holds a US patent on the technology.

Osteopathic manual treatment and ultrasound therapy for chronic low back pain: a randomized controlled trial.

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PURPOSE We studied the efficacy of osteopathic manual treatment (OMT) and ultrasound therapy (UST) for chronic low back pain. METHODS A randomized, double-blind, sham-controlled, 2 x 2 factorial design was used to study OMT and UST for short-term relief of nonspecific chronic low back pain. The 455 patients were randomized to OMT (n = 230) or sham OMT (n = 225) main effects groups, and to UST (n = 233) or sham UST (n = 222) main effects groups. Six treatment sessions were provided over 8 weeks. Intention-to-treat analysis was performed to measure moderate and substantial improvements in low back pain at week 12 (30% or greater and 50% or greater pain reductions from baseline, respectively). Five secondary outcomes, safety, and treatment adherence were also assessed. RESULTS There was no statistical interaction between OMT and UST. Patients receiving OMT were more likely than patients receiving sham OMT to achieve moderate (response ratio [RR] = 1.38; 95% CI, 1.16-1.64; P <.001) and substantial (RR = 1.41, 95% CI, 1.13-1.76; P = .002) improvements in low back pain at week 12. These improvements met the Cochrane Back Review Group criterion for a medium effect size. Back-specific functioning, general health, work disability specific to low back pain, safety outcomes, and treatment adherence did not differ between patients receiving OMT and sham OMT. Nevertheless, patients in the OMT group were more likely to be very satisfied with their back care throughout the study (P <.001). Patients receiving OMT used prescription drugs for low back pain less frequently during the 12 weeks than did patients in the sham OMT group (use ratio = 0.66, 95% CI, 0.43-1.00; P = .048). Ultrasound therapy was not efficacious. CONCLUSIONS The OMT regimen met or exceeded the Cochrane Back Review Group criterion for a medium effect size in relieving chronic low back pain. It was safe, parsimonious, and well accepted by patients.

Source: Annals of Family Medicine

 

Therapeutic ultrasound for carpal tunnel syndrome..

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Therapeutic ultrasound may be offered to people experiencing mild to moderate symptoms of carpal tunnel syndrome (CTS). The effectiveness and duration of benefit of this non-surgical intervention remain unclear.

OBJECTIVES: To review the effects of therapeutic ultrasound compared with no treatment, placebo or another non-surgical intervention in people with CTS. SEARCH
METHODS: On 27 November 2012, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (2012, Issue 11 in The Cochrane Library), MEDLINE (January 1966 to November 2012), EMBASE (January 1980 to November 2012), CINAHL Plus (January 1937 to November 2012), and AMED (January 1985 to November 2012).
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any regimen of therapeutic ultrasound with no treatment, a placebo or another non-surgical intervention in people with CTS.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias in the included studies. We calculated risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CIs) for primary and secondary outcomes. We pooled results of clinically homogenous trials in a meta-analysis using a random-effects model, where possible, to provide estimates of the effect.
MAIN RESULTS: We included 11 studies including 414 participants in the review. Two trials compared therapeutic ultrasound with placebo, two compared one ultrasound regimen with another, two compared ultrasound with another non-surgical intervention, and six compared ultrasound as part of a multi-component intervention with another non-surgical intervention (for example, exercises and splint). The risk of bias was low in some studies and unclear or high in other studies, with only two reporting that the allocation sequence was concealed and six reporting that participants were blinded. Overall, there is insufficient evidence that one therapeutic ultrasound regimen is more efficacious than another. Only two studies reported the primary outcome of interest, short-term overall improvement (any measure in which patients indicate the intensity of their complaints compared with baseline, for example, global rating of improvement, satisfaction with treatment, within three months post-treatment). One low quality trial with 68 participants found that when compared with placebo, therapeutic ultrasound may increase the chance of experiencing short-term overall improvement at the end of seven weeks treatment (RR 2.36; 95% CI 1.40 to 3.98), although losses to follow-up and failure to adjust for the correlation between wrists in participants with bilateral CTS in this study suggest that this data should be interpreted with caution. Another low quality trial with 60 participants found that at three months post-treatment therapeutic ultrasound plus splint increased the chance of short-term overall improvement (patient satisfaction) when compared with splint alone (RR 3.02; 95% CI 1.36 to 6.72), but decreased the chance of short-term overall improvement when compared with low-level laser therapy plus splint (RR 0.87; 95% CI 0.57 to 1.33), though participants were not blinded to treatment, it was unclear if the random allocation sequence was adequately concealed, and there was a potential unit of analysis error. Differences between groups receiving different frequencies and intensities of ultrasound, and between ultrasound as part of a multi-component intervention versus other non-surgical interventions, were generally small and not statistically significant for symptoms, function, and neurophysiologic parameters. No studies reported any adverse effects of therapeutic ultrasound, but this outcome was only measured in three studies. More adverse effects data are required before any firm conclusions on the safety of therapeutic ultrasound can be made.
AUTHORS’ CONCLUSIONS: There is only poor quality evidence from very limited data to suggest that therapeutic ultrasound may be more effective than placebo for either short- or long-term symptom improvement in people with CTS. There is insufficient evidence to support the greater benefit of one type of therapeutic ultrasound regimen over another or to support the use of therapeutic ultrasound as a treatment with greater efficacy compared to other non-surgical interventions for CTS, such as splinting, exercises, and oral drugs. More methodologically rigorous studies are needed to determine the effectiveness and safety of therapeutic ultrasound for CTS.

Source: cochrane