EASI Access II --- Follow-up Study to the EASI Access Trial

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00740727
• Collaborator: Baxter Healthcare Corporation (Industry)
• Enrollment: 18
• Location: 1
• Arm: 1
• Duration (Days): 28
• Patients Per Site Per Month: 19.6

Study Details

Study Description

Brief Summary

Test whether Basic Life Support (BLS) providers can successfully place Enzymatically Augmented Subcutaneous Infusion (EASI) Access lines for subcutaneous infusion, and characterize intravascular absorption of EASI-administered (tracer-labelled) glucose (D5W).

Condition or Disease	Intervention/Treatment	Phase
Disaster Medicine; Difficult Intravenous Access; Dehydration	Drug: Human recombinant hyaluronidase (HRH); Procedure: Enzymatically Augmented Subcutaneous Infusion (EASI) line placement	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Enzymatically Augmented Subcutaneous Infusion (EASI) Access II Trial
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EASI Subjects will undergo placement of EASI catheters. All subjects in whom EASI catheters are placed, will receive Human Recombinant Hyaluronidase (HRH) as part of the EASI placement. (No subject will receive HRH, other than as part of EASI catheter placement.)	Drug: Human recombinant hyaluronidase (HRH); 150u HRH administered via EASI access line, prior to infusion of 250 D5W (5% dextrose in water); Other Names: Hylenex ; Procedure: Enzymatically Augmented Subcutaneous Infusion (EASI) line placement; Subjects will under placement of an EASI line. This entails placement of a small (20-gauge) catheter in the upper back, in the subcutaneous space.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Successfully Placed EASI Lines [1 day]

   Ability of Basic Life Support (BLS) providers to place EASI access lines. The unit of analysis is the 18 BLS participants (these were also the 18 individuals in whom the EASI access lines were placed).

2. Systemic Absorption of Subcutaneously Administered Tracer-labelled Glucose [1 day]

   Number of subjects (out of a possible 18) in whom EASI-administered tracer-labeled glucose was absorbed systemically.Gas chromatography/Mass spectrometry analysis was performed on timed phlebotomy samples, to assess for tracer-labeled glucose.Isotopic glucose enrichment was determined by plasma analysis on a Hewlett-Packard 5985B quadruple mass spectrometer, using + chemical ionization (methane reagent gas). A 12m×0.20mm ID, OV-1 capillary column (He carrier) was used in the gas chromatograph.Enrichments of glucose were calculated as atom percent excess relative to natural background level.

Secondary Outcome Measures

1. Number of Participants With Pain During EASI Infusion [1 day]

   Assessment during EASI placement & initial infusion, for pain as assessed with 10-point scale (0=no pain; 10=worst pain). Significant pain was defined a priori as a pain score of at least 3.

2. Number of Participants With Pain at EASI Infusion Site, on Next-day Follow-up [2 days]

   Assessment during upon next-day follow-up, for pain as assessed with 10-point scale (0=no pain; 10=worst pain). Significant pain was defined a priori as a pain score of at least 3. Presence of any pain (yes or no question and then numeric rating if pain was present) was assessed upon follow-up by telephone; on this follow-up a yes/no question was also asked about any complications at infusion site (in the upper back).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects will be at least 18 years of age and have none of the following conditions:

• pregnancy (negative urine pregnancy test to be performed before study participation),

• diabetes, or coagulopathic (including taking any anticoagulants);

• Subjects cannot be taking steroids or other immunosuppressants.

• Because of the potential for reduced hyaluronidase effectiveness, the study excludes patients taking more than 80 mg daily aspirin, as well as any patients taking ACTH, antihistamines, or estrogen other than in oral contraceptive preparations.

• Subjects will not be required to fast before the study, but will not allowed to eat or drink during the EASI infusion or the phlebotomy sampling time frame.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• Baxter Healthcare Corporation

Investigators

• Principal Investigator: Stephen H Thomas, MD MPH, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• Alam HB, Rhee P. New developments in fluid resuscitation. Surg Clin North Am. 2007 Feb;87(1):55-72, vi. Review.
• Beylot M, David F, Brunengraber H. Determination of the 13C-labeling pattern of glutamate by gas chromatography-mass spectrometry. Anal Biochem. 1993 Aug 1;212(2):532-6.
• Bijur PE, Latimer CT, Gallagher EJ. Validation of a verbally administered numerical rating scale of acute pain for use in the emergency department. Acad Emerg Med. 2003 Apr;10(4):390-2.
• Bookbinder LH, Hofer A, Haller MF, Zepeda ML, Keller GA, Lim JE, Edgington TS, Shepard HM, Patton JS, Frost GI. A recombinant human enzyme for enhanced interstitial transport of therapeutics. J Control Release. 2006 Aug 28;114(2):230-41. Epub 2006 Jun 7.
• Craig AS, Eikenberry EF, Parry DA. Ultrastructural organization of skin: classification on the basis of mechanical role. Connect Tissue Res. 1987;16(3):213-23.
• Dalal S, Bruera E. Dehydration in cancer patients: to treat or not to treat. J Support Oncol. 2004 Nov-Dec;2(6):467-79, 483. Review.
• Frost GI. Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration. Expert Opin Drug Deliv. 2007 Jul;4(4):427-40. Review.
• Laurent UB, Dahl LB, Reed RK. Catabolism of hyaluronan in rabbit skin takes place locally, in lymph nodes and liver. Exp Physiol. 1991 Sep;76(5):695-703.
• Sever MS, Vanholder R, Lameire N. Management of crush-related injuries after disasters. N Engl J Med. 2006 Mar 9;354(10):1052-63. Review.
• Stafford PW, Blinman TA, Nance ML. Practical points in evaluation and resuscitation of the injured child. Surg Clin North Am. 2002 Apr;82(2):273-301.
• Thomas JR, Yocum RC, Haller MF, von Gunten CF. Assessing the role of human recombinant hyaluronidase in gravity-driven subcutaneous hydration: the INFUSE-LR study. J Palliat Med. 2007 Dec;10(6):1312-20.

• ClinicalTrials.gov Identifier: NCT00740727
• Other Study ID Numbers: EASI Access II
• First Posted: Aug 25, 2008
• Last Update Posted: Sep 11, 2009
• Last Verified: Sep 1, 2009

• Keywords provided by , ,: Disaster; Mass casualty incident; Prehospital; Rehydration; Intravascular access
• Additional relevant MeSH terms: Dehydration

Study Results

Participant Flow

Recruitment Details	Recruitment occurred in January 2009
Pre-assignment Detail	A total of 20 subjects were consented. The study day ran long, so 2 subjects who had consented (and had an initial intravenous {IV} access placed, but no EASI access placed) declined to have any of the study procedures performed since the 2-hour phlebotomy window would have kept them at the study site until the evening.

Arm/Group Title	EASI/HRH(Human Recombinant Hyaluronidase)
Arm/Group Description	Subjects underwent placement of EASI (Enzymatically Augmented Subcutaneous Infusion) catheters
Period Title: Overall Study
STARTED	18
COMPLETED	18
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	EASI/HRH(Human Recombinant Hyaluronidase)
Arm/Group Description	Subjects underwent placement of EASI (Enzymatically Augmented Subcutaneous Infusion) catheters
Overall Participants	18
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	18 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25 (7)
Sex: Female, Male (Count of Participants)
Female	3 16.7%
Male	15 83.3%
Region of Enrollment (participants) [Number]
United States	18 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Successfully Placed EASI Lines
Description	Ability of Basic Life Support (BLS) providers to place EASI access lines. The unit of analysis is the 18 BLS participants (these were also the 18 individuals in whom the EASI access lines were placed).
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

Participants received EASI access placement, with co-administration of human recombinant hyaluronidase.

Arm/Group Title	EASI/HRH(Human Recombinant Hyaluronidase)
Arm/Group Description	Subjects underwent placement of EASI (Enzymatically Augmented Subcutaneous Infusion) catheters
Measure Participants	18
Number [Participants]	18 100%

2. Primary Outcome

Title	Systemic Absorption of Subcutaneously Administered Tracer-labelled Glucose
Description	Number of subjects (out of a possible 18) in whom EASI-administered tracer-labeled glucose was absorbed systemically.Gas chromatography/Mass spectrometry analysis was performed on timed phlebotomy samples, to assess for tracer-labeled glucose.Isotopic glucose enrichment was determined by plasma analysis on a Hewlett-Packard 5985B quadruple mass spectrometer, using + chemical ionization (methane reagent gas). A 12m×0.20mm ID, OV-1 capillary column (He carrier) was used in the gas chromatograph.Enrichments of glucose were calculated as atom percent excess relative to natural background level.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

Participants received EASI access placement, with co-administration of human recombinant hyaluronidase.

Arm/Group Title	EASI/HRH(Human Recombinant Hyaluronidase)
Arm/Group Description	Subjects underwent placement of EASI (Enzymatically Augmented Subcutaneous Infusion) catheters
Measure Participants	18
Number [Participants]	18 100%

3. Secondary Outcome

Title	Number of Participants With Pain During EASI Infusion
Description	Assessment during EASI placement & initial infusion, for pain as assessed with 10-point scale (0=no pain; 10=worst pain). Significant pain was defined a priori as a pain score of at least 3.
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

Participants received EASI access placement, with co-administration of human recombinant hyaluronidase.

Arm/Group Title	EASI/HRH(Human Recombinant Hyaluronidase)
Arm/Group Description	Subjects underwent placement of EASI (Enzymatically Augmented Subcutaneous Infusion) catheters
Measure Participants	18
Number [Participants]	2 11.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EASI/HRH(Human Recombinant Hyaluronidase)
	Comments	This analysis reports the number of subjects (of 18 possible) who experienced pain, during EASI placement or infusion, at the a priori-defined level of at least 3 on a 10-point pain scale.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	% of subjects with infusion pain
	Estimated Value	11.1
	Confidence Interval	() 95%; 1.4 to 34.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants With Pain at EASI Infusion Site, on Next-day Follow-up
Description	Assessment during upon next-day follow-up, for pain as assessed with 10-point scale (0=no pain; 10=worst pain). Significant pain was defined a priori as a pain score of at least 3. Presence of any pain (yes or no question and then numeric rating if pain was present) was assessed upon follow-up by telephone; on this follow-up a yes/no question was also asked about any complications at infusion site (in the upper back).
Time Frame	2 days

Outcome Measure Data

Analysis Population Description

Participants received EASI access placement, with co-administration of human recombinant hyaluronidase.

Arm/Group Title	EASI/HRH(Human Recombinant Hyaluronidase)
Arm/Group Description	Subjects underwent placement of EASI (Enzymatically Augmented Subcutaneous Infusion) catheters
Measure Participants	18
Number [Participants]	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	EASI/HRH(Human Recombinant Hyaluronidase)
	Comments	This analysis reports the number of subjects (of 18 possible) who experienced pain, as assessed on next-day follow-up (24 hours after EASI infusion), at the a priori-defined level of at least 3 on a 10-point pain scale.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	% subjects with next-day EASI site pain
	Estimated Value	0
	Confidence Interval	() 97.5%; 0 to 18.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.