Trial Outcomes & Findings for Comparison of 4.0 mg/kg Sugammadex at 1-2 Post Tetanic Counts (PTC) in Renal or Control Patients (19.4.328)(P05769) (NCT NCT00702715)

Last Updated: 2017-05-16

Results Overview

Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

69 participants

Primary outcome timeframe

start of administration of sugammadex to recovery from neuromuscular blockade

Results posted on

2017-05-16

Participant Flow

Participant milestones

Participant milestones
Measure	Participants With Severe Renal Impairment Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 post-tetanic counts (PTC). Severe renal impairment was defined as creatinine clearance \<30mL/min.	Participants With Normal Renal Function Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance \>=80mL/min.
Overall Study STARTED	35	33
Overall Study COMPLETED	34	33
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Participants With Severe Renal Impairment Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 post-tetanic counts (PTC). Severe renal impairment was defined as creatinine clearance \<30mL/min.	Participants With Normal Renal Function Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance \>=80mL/min.
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

Comparison of 4.0 mg/kg Sugammadex at 1-2 Post Tetanic Counts (PTC) in Renal or Control Patients (19.4.328)(P05769)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Participants With Severe Renal Impairment n=35 Participants Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Severe renal impairment was defined as creatinine clearance \<30mL/min.	Participants With Normal Renal Function n=33 Participants Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance \>=80mL/min.	Total n=68 Participants Total of all reporting groups
Age, Continuous	57 years STANDARD_DEVIATION 16 • n=5 Participants	45 years STANDARD_DEVIATION 15 • n=7 Participants	51 years STANDARD_DEVIATION 16 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	13 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	20 Participants n=7 Participants	38 Participants n=5 Participants

PRIMARY outcome

Timeframe: start of administration of sugammadex to recovery from neuromuscular blockade

Population: Analysis performed using the Intent-to-Treat (ITT) Population, which consisted of all treated subjects who had at least one efficacy measurement.

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment n=35 Participants Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Severe renal impairment was defined as creatinine clearance \<30mL/min.	Participants With Normal Renal Function n=32 Participants Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance \>=80mL/min.
Time to Recovery of the T4/T1 Ratio to 0.9.	205 seconds Interval 169.0 to 248.0	112 seconds Interval 92.0 to 138.0

SECONDARY outcome

Timeframe: start of administration of sugammadex to recovery from neuromuscular blockade

Population: Analysis performed using the Intent-to-Treat (ITT) Population, which consisted of all treated subjects who had at least one efficacy measurement.

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment n=35 Participants Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Severe renal impairment was defined as creatinine clearance \<30mL/min.	Participants With Normal Renal Function n=32 Participants Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance \>=80mL/min.
Time to Recovery of the T4/T1 Ratio to 0.8	169 seconds Interval 141.0 to 203.0	90 seconds Interval 76.0 to 107.0

SECONDARY outcome

Timeframe: start of administration of sugammadex to recovery from neuromuscular blockade

Population: Analysis performed using the Intent-to-Treat (ITT) Population, which consisted of all treated subjects who had at least one efficacy measurement.

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment n=35 Participants Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Severe renal impairment was defined as creatinine clearance \<30mL/min.	Participants With Normal Renal Function n=32 Participants Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance \>=80mL/min.
Time to Recovery of T4/T1 Ratio to 0.7	144 seconds Interval 120.0 to 172.0	79 seconds Interval 67.0 to 92.0

Adverse Events

Participants With Severe Renal Impairment

Serious events: 9 serious events

Other events: 14 other events

Deaths: 0 deaths

Participants With Normal Renal Function

Serious events: 3 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Participants With Severe Renal Impairment n=35 participants at risk Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Severe renal impairment was defined as creatinine clearance \<30mL/min.	Participants With Normal Renal Function n=33 participants at risk Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance \>=80mL/min.
Infections and infestations Pneumonia	2.9% 1/35 • Number of events 1	0.00% 0/33
Infections and infestations Subdiaphragmatic abscess	0.00% 0/35	3.0% 1/33 • Number of events 1
Infections and infestations Thrombophlebitis septic	2.9% 1/35 • Number of events 1	0.00% 0/33
Injury, poisoning and procedural complications Anastomotic leak	0.00% 0/35	3.0% 1/33 • Number of events 1
Injury, poisoning and procedural complications Incision site haematoma	2.9% 1/35 • Number of events 1	0.00% 0/33
Injury, poisoning and procedural complications Narcotic intoxication	2.9% 1/35 • Number of events 1	0.00% 0/33
Injury, poisoning and procedural complications Seroma	0.00% 0/35	3.0% 1/33 • Number of events 1
Injury, poisoning and procedural complications Wound	2.9% 1/35 • Number of events 1	0.00% 0/33
Injury, poisoning and procedural complications Wound haemorrhage	5.7% 2/35 • Number of events 2	0.00% 0/33
Investigations Blood creatinine increased	2.9% 1/35 • Number of events 1	0.00% 0/33
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign ovarian tumour	2.9% 1/35 • Number of events 1	0.00% 0/33
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.00% 0/35	3.0% 1/33 • Number of events 1
Renal and urinary disorders Azotaemia	2.9% 1/35 • Number of events 1	0.00% 0/33
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	2.9% 1/35 • Number of events 1	0.00% 0/33
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.9% 1/35 • Number of events 1	0.00% 0/33
Vascular disorders Extremity necrosis	2.9% 1/35 • Number of events 1	0.00% 0/33

Other adverse events

Other adverse events
Measure	Participants With Severe Renal Impairment n=35 participants at risk Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Severe renal impairment was defined as creatinine clearance \<30mL/min.	Participants With Normal Renal Function n=33 participants at risk Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance \>=80mL/min.
Blood and lymphatic system disorders Anaemia	8.6% 3/35 • Number of events 3	0.00% 0/33
Gastrointestinal disorders Nausea	8.6% 3/35 • Number of events 3	0.00% 0/33
Gastrointestinal disorders Vomiting	5.7% 2/35 • Number of events 2	0.00% 0/33
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/35	6.1% 2/33 • Number of events 2
Injury, poisoning and procedural complications Procedural hypertension	0.00% 0/35	6.1% 2/33 • Number of events 2
Injury, poisoning and procedural complications Procedural hypotension	11.4% 4/35 • Number of events 5	3.0% 1/33 • Number of events 1
Injury, poisoning and procedural complications Procedural nausea	2.9% 1/35 • Number of events 1	9.1% 3/33 • Number of events 3
Injury, poisoning and procedural complications Procedural pain	25.7% 9/35 • Number of events 9	33.3% 11/33 • Number of events 13
Investigations Neutrophil count increased	0.00% 0/35	6.1% 2/33 • Number of events 2

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee All published results will be based on validated data released by the sponsor and must include one sponsor author. There may be one author from each investigational site, provided that the criteria for authorship are met. In case the proposed publication contains reference to an invention owned by sponsor or to which sponsor otherwise has rights, the sponsor may request a reasonable suspension of the publication in order to be able to file a patent application protecting such invention.
Publication restrictions are in place

Restriction type: OTHER