Conference Coverage

Remimazolam surpasses midazolam for bronchoscopy sedation

 

Key clinical point: Remimazolam, an investigational sedative, showed faster onset and offset compared with midazolam and also resulted in significantly more successful bronchoscopy procedures.

Major finding: The rate of successful bronchoscopies was 83% with remimazolam, 34% with midazolam, and 5% with placebo.

Data source: A multicenter, phase III trial with 431 patients.

Disclosures: The trial was funded by Paion, the company developing remimazolam. Dr. Silvestri and Dr. Stanbrook had no relevant disclosures.

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Comment by Eric Gartman, MD, FCCP

Dr. Eric J. Gartman
Dr. Eric J. Gartman
This medication may represent a valuable addition to our options for moderate sedation during procedures - in that its main benefit seems to be in its onset of sedation. It will be important to assess this study's outcome data once published - especially with regard to the driver of the differences seen between groups in the composite primary outcome (i.e., successfully completing a procedure would be the important primary endpoint to most, and we should be interested to see if it was the dosing/time-based outcomes that drove the primary outcome differences between the groups). Further, if there are significant cost differences between these two medications, this will certainly limit their incorporation into practice unless there are significant differences in patient-centered outcomes.


 

AT CHEST 2017

– An investigational sedative, remimazolam, that’s similar to midazolam but with faster onset and offset, resulted in significantly better procedural success compared with midazolam in a multicenter, phase III trial with 431 patients.

The results also showed that remimazolam was as safe as midazolam (Versed), with a very similar adverse event profile, said Gerard A. Silvestri, MD, FCCP, at the CHEST annual meeting.

Dr, Gerard A. Silvestri Mitchel L. Zoler/Frontline Medical News
Dr. Gerard A. Silvestri
Paion, the company developing remimazolam, plans to combine data from this bronchoscopy study with data collected from other procedural studies that included patients undergoing colonoscopy and upper gastrointestinal endoscopy, and seek U.S. Food & Drug Administration approval for the drug in 2018, according to a written statement.

The bronchoscopy trial enrolled patients at any of 15 U.S. centers with an American Society of Anesthesiologists (ASA) physical status classification of I-III and scheduled for diagnostic or therapeutic bronchoscopy. The enrolled patients averaged 62 years of age, and 38% were in ASA class III.

All patients received initial sedation treatment with fentanyl, followed by a three-to-one randomization to blinded remimazolam, blinded placebo that included midazolam rescue, or open-label midazolam. The study’s primary efficacy endpoint was procedural success, defined as patients who underwent the complete procedure without need for an alternative sedative and without need for more than five doses of the patient’s assigned medication within any 15 minute period during the procedure or need for more than three midazolam doses within any 12-minute period in the patients randomized to receive midazolam.

This primary endpoint occurred in 83% of 303 patients in the remimazolam arm, 5% of 59 patients in the placebo arm, and 34% of 69 patients in the midazolam arm, a statistically significant difference between the remimazolam patients and each of the comparator groups, reported Dr. Silvestri, a professor of medicine and a lung cancer pulmonologist at the Medical University of South Carolina in Charleston.

The results also demonstrated the faster inset and offset of remimazolam. Treatment achieved adequate sedation to start the procedure after a median of 5 minutes with remimazolam, a median of 15.5 minutes with midazolam, and a median of 17 minutes among patients in the placebo group. Once sedation finished, patients returned to being fully alert after a median of 6 minutes with remimazolam, a median of 12 minutes with midazolam, and a median of 13.5 minutes for patients in the placebo arm.

“What’s nice about remimazolam is that the adverse event profile is exactly the same as with placebo and midazolam, and you have a reversal agent,” the same as what’s used for midazolam, he said.

Dr. Matthew B. Stanbrook pulmonologist at the University of Toronto Mitchel L. Zoler/Frontline Medical News
Dr. Matthew B. Stanbrook
Midazolam is the current “workhorse” sedative, but “we can do better,” commented Matthew B. Stanbrook, MD, a pulmonologist at the University of Toronto. “There would be some benefit from a sedative with faster onset and offset,” he said in an interview.

Dr. Silvestri suggested several additional studies he would like to see run on remimazolam to better understand its clinical performance and role. These include studying the drug in the elderly, patients with an ASA classification of IV, obese patients, and those on high narcotic doses. He also suggested comparing remimazolam directly with propofol, testing remimazolam as a stand-alone agent without fentanyl co-administration, and trying the drug during other pulmonary procedures such as pleural-catheter placement and other invasive procedures, and in ICU patients.

The trial was funded by Paion, the company developing remimazolam. Dr. Silvestri and Dr. Stanbrook had no relevant disclosures.

On Twitter @mitchelzoler

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