ECYPVEN-H/17: Clinical Trial to Assess the Effectiveness of Applying Dry Local Heat and/ or High Tourniquet Pressure for Venipuncture.

• Sponsor: Universidad Complutense de Madrid (Other)
• Overall Status: Completed
• CT.gov ID: NCT04027218
• Collaborator: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa (Other)
• Enrollment: 62
• Location: 1
• Arms: 3
• Actual Duration (Months): 8.8
• Patients Per Site Per Month: 7

Study Details

Study Description

Brief Summary

Low level intervention health products clinical trial, fourth phase, non-commercial research. Dissertation of COMPLUTENSE UNIVERSITY of Madrid.

Principal Investigator of this clinical trial: Ms. LETICIA CARMEN SIMÓN LÓPEZ Collaborative investigators: Dr. DOLORES OCHOA-MAZARRO (principal investigator of bioequivalence clinical trial), and Sir. SERGIO LUQUERO-BUENO (collaborative researcher)

The setting is Clinical trials Unit of Clinical Pharmacology Department. LA PRINCESA HOSPITAL of Madrid. Research Ethical Committee of LA PRINCESA HOSPITAL of Madrid. Any person will monitor this clinical trial because the sponsor and principal researcher are the same person. Nevertheless, an adherence to this protocol will ensure by principal researcher and co-researchers.

The three interventions are:

1. To Apply local dry heat.

2. To apply high tourniquet pressure.

3. To apply both of them. (Dry heat and high pressure) The common comparator: Current Clinical practice for peripheral venous catheterization.

The main hypothesis: The number of attempts of success venipuncture at first time are influenced by any of the interventions applied before.

The main goal: To identify the most effective intervention of applying dry local heat and/or high tourniquet pressure in relation of number success venipuncture attempts, compared to current clinical practice.

Design: An experimental, randomized study which is controlled with current clinical practice to insert a peripheral vein catheter. It is an incomplete cross-over clinical trial, with three arms which are involved interventions and a common comparator.

Population: Adult healthy subjects. Sample size: It is required to enroll 54 subjects with a 95% of level of confidence and 80% level of power.

Main variable: Succeed peripheral vein catheter insertion at first attempt.

Effectiveness assessment: The optimal effectiveness is considered when vein cannulation success at first attempt exceeds 95% applying any of the interventions.

Planned date to address: It is planned to carry out around June and/or July of 2017 for the main variable.

Condition or Disease	Intervention/Treatment	Phase
Venipuncture; Healthy Adult	Device: Dry heat; Device: High pressure; Device: Combination of dry heat and high pressure	N/A

Detailed Description

The study is considered a low level intervention clinical trial to evaluate the use and safety of a sanitary product marketed and accredited for a different aim, but according to their rules of using.

It is experimental, randomized and controlled study with the usual technique of inserting a venipuncture catheter until now. Incomplete clinical trial, blind to third parties, in healthy volunteers, which consists of three arms, in which they are intervened and the comparator is applied. The volunteers comes from a bioequivalence clinical trial for testing a new drug, and a venous catheter is required in two period between a wash-out period of one week, approximately.

For each volunteer one of intervention is applied in one period, and in other period the comparator is applied. Thus, one intervention and the sequence of one intervention application and comparator is assigned by randomization using sealed envelopes. Randomization is only performed in first period, in second period one intervention or comparator assigned in applied. Thus, each one volunteer is her/his own comparator

. Before assigned intervention or comparator is applied, a Venous International Assessment is carried out using Venous International Assessment (VIA) validated scale by nurse perception and palpation. After assigned intervention, another VIA is performed. Then, when peripheral venous catheterization is achieved, a blood sample is withdrawn in order to examine hemolysis. Afterwards, pain is registered by Visual Analogue Scale (VAS) validated scale within no more than two hours from vein catheterization, and skin perception is evaluated by Fitzpatrick's scale (only in first period) in order to analyze a possible relationship with adverse events on skin. Subjects are followed-up for 72h in order to monitor adverse events if applicable.

According to hemolysis, an ethylene diamine tetra acetate (EDTA) blood sample is processing at 3400 revolutions per minute at 4 Celsius grades for 10 minutes, and plasma samples are frosted for 24-48h. Afterwards, they are defrosted, and analyzed by absorbance using NANODROP SPECTROPHOTOMETER. The analysis by spectrophotometer is blinded of intervention or comparator used to withdrawn.

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Experimental, randomized and controlled study with the usual technique of inserting a venipuncture catheter until now. Incomplete clinical trial, blind to third parties, in healthy volunteers, which consists of three arms, in which they are intervened and the comparator is applied.Experimental, randomized and controlled study with the usual technique of inserting a venipuncture catheter until now. Incomplete clinical trial, blind to third parties, in healthy volunteers, which consists of three arms, in which they are intervened and the comparator is applied.
• Masking: Single (Investigator)
• Masking Description: For hemolysis analysis in blood samples, the responsible of analysis by spectrophotometry is blinded from the intervention or comparator used for blood sample performed, using two different departments: one for interventions and comparator applications and other for spectrophotometer.
• Primary Purpose: Supportive Care
• Official Title: Cross-over Clinical Trial to Assess the Effectiveness of Applying Dry Local Heat and/ or High Tourniquet Pressure With Current Clinical Practice for Venipuncture, and Blinded for Evaluating Their Impact on Hemolysis
• Actual Study Start Date: Jul 9, 2017
• Actual Primary Completion Date: Jul 23, 2017
• Actual Study Completion Date: Apr 3, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Current clinical practice-Dry heat The standardized and approved Clinical and Laboratory Standards Institute (CLSI) GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital. 1 period (current clinical practice) and 2 period (dry heat) or 1 period (dry heat) and 2 period (current clinical practice).	Device: Dry heat; The application is made with two sacks of carob seeds during 7 minutes. The sacks are placed on antebrachial anatomical zone, together, and previously heated in the microwave for 0.30 seconds at 850 W of power.
Active Comparator: Current clinical practice- Hihg pressure The standardized and approved CLSI GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital. 1 period (current clinical practice) and 2 period (high pressure) or 1 period (high pressure) and 2 period (current clinical practice).	Device: High pressure; It will be carried out with the use of the manual aneroid sphygmomanometer fixed at 100 millimeters of mercury. Brand (QUIRUMED) with European Conformity (CE) marking 0197. A pressure lower than the systolic blood pressure, and in each subject will be monitored the radial pulse.
Active Comparator: Current clinical practice-Combination The standardized and approved CLSI GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital. 1 period (current clinical practice) and 2 period (combination of dry heat and high pressure) or 1 period (combination of dry heat and high pressure) and 2 period (current clinical practice).	Device: Combination of dry heat and high pressure; The application is made with two sacks of carob seeds during 7 minutes. The sacks may be placed on antebrachial anatomical zone, together, and previously heated in the microwave for 0.30 seconds at 850 W of power; according to instructions for use. After 7 minutes, the pressure is applied with the use of the manual aneroid sphygmomanometer fixed at 100 millimeters of mercury. Brand QUIRUMED with CE Marking 0197. A pressure lower than the systolic blood pressure, and in each subject will be monitored the radial pulse.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Successful Venous Catheterization at the First Attempt [From 1-5 minutes]

   Number of participants with successful venous catheterization at the first attempt (effectiveness)

Secondary Outcome Measures

1. Number of the Grade of Venous International Assessment (VIA) Scale After Application of Intervention [up to ten minutes after application of intervention]

   Vein perception in VIA scale was considered as the self-reported visual observation or palpation of a venous pathway. Subjects were graded using the current clinical practice vein stagnation with an elastic compressor application (Unidix®). Five grades considering the numbers of points of optimal puncture visible and tangible, in one of the dorsal veins of the hand, forearm cephalic and/or basilic. Grade I: At least six. Grade II: At least four. Grade III: At least three. Grade IV: At least one. Grade V: None. Therefore, the best grade is I, and the worst grade is V. Higher scores mean a worse outcome.

2. Number of the Grade in Visual Analogue Scale (VAS) for Pain After Intervention [up to 2 hours after application of intervention]

   Visual Analogue Scale (VAS) in pain was measured by integer number. Pain was self-expressed by participants, in a range from 0 to 10. 10: was considered the worst pain experienced 0: no pain perceived. The entire range was 0, 1, 2, 3, 4, 5 , 6, 7, 8, 9, 10. Therefore, higher scores mean a worse outcome.

3. Number of Participants in Each Type of Skin Standardized According to Fitzpatrick Scale [up to 2 hours after application of intervention]

   Number of participants in each type of skin standardized according to Fitzpatrick scale. Fitzpatrick scale is the UNABBREVIATED scale that indicates different types of skin described as "phototypes". The individuals were graded clinically by sel-expressed by participants in the area of the forearm not exposed to the sun. In a range of six phototypes, where phototype I corresponds with the minimum and phototype VI the maximum. Phototype I: Ivory white, burns easily, never tans. Phototype II: White, burns easily, tans minimally with difficulty. Phototype III: White, burns moderately, tans moderately and uniformly Phototype IV: Beige-olive, lightly tanned, burns minimally, tans moderately and easily. Phototype V: Rarely burns, tans profusely. Phototype VI: Dark brown or black, never burns, tans profusely. Phototype I was considered more risky outcome for expected adverse events in skin. None was considered better or worse outcome.

4. Level of Hemolysis in Absorbance Units [up to 9 days after first intervention completion]

   Detection level of absorbance values of hemolysis in plasma samples. The units of absorbance are dimensionless. The hemolysis in plasma is analyzed by spectrophotometry method, using a NanoDrop® 2000 Spectrophotometer device (Thermo Fisher Scientific Inc., Wilmington, United States of America). The following equation was used to correct lipemia: (A414-A385) +0.16xA385. Additionally, a baseline correction factor at 750 nanometer wavelength was applied. Therefore, absorbance were measured at 414 nanometer, 385 nanometer and 750 nanometer. Higher values represent a worse outcome: higher value mean higher hemolysis in a blood sample. Therefore, lower values, near to zero are better outcomes that mean low hemolysis in blood sample.

5. Number of Participants With Adverse Events [During the study completion,. an average of 30 days.]

   Number of adverse events by visual inspection.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Signed the informed consent form for bioequivalence study

• Signed the informed consent form for this clinical trial

• Fluid intake of participants was limited to a volume equal to or less than 500 ml

• Participants fasted 6-8 hours before venous cannulation

• Body mass index (BMI) between 18.5-29.9

• Vein perception by Venous International Assessment (VIA) scale between 5 to 2 grade.

Exclusion Criteria:

• Grade one in VIA scale

• Smokers

• BMI lower than 18.5 or equivalent or higher than 30

• Subjects who had any disease,

• Blood test, urinalysis, physical examination or electrocardiogram showing disorders with clinical relevance

• Subjects receiving treatment for anything apart from contraceptives.

• Gluten, lactose intolerance, vegetarian or vegan subjects for bioequivalence subjects.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Leticia Carmen Simón López	Madrid		Spain	28006

Sponsors and Collaborators

• Universidad Complutense de Madrid
• Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Investigators

• Principal Investigator: Leticia Carmen Simón López, RN, Universidad Complutense de Madrid

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Jun 22, 2017

More Information

Publications

• de la Torre-Montero JC, Montealegre-Sanz M, Faraldo-Cabana A, Oliva-Pellicer B, García-Real I, Fenwick M, Marcos Cáceres E, Rivas-Eguía B, Vila-Borrajo C, Valles-Andrés J, Alonso-Gordoa T, García-Carrión C, Diaz-Rubio García E, Beneit-Montesinos JV. Venous International Assessment, VIA scale, validated classification procedure for the peripheral venous system. J Vasc Access. 2014 Jan-Feb;15(1):45-50. doi: 10.5301/jva.5000173. Epub 2013 Sep 4.
• Eilers S, Bach DQ, Gaber R, Blatt H, Guevara Y, Nitsche K, Kundu RV, Robinson JK. Accuracy of self-report in assessing Fitzpatrick skin phototypes I through VI. JAMA Dermatol. 2013 Nov;149(11):1289-94. doi: 10.1001/jamadermatol.2013.6101.
• Ferreira-Valente MA, Pais-Ribeiro JL, Jensen MP. Validity of four pain intensity rating scales. Pain. 2011 Oct;152(10):2399-2404. doi: 10.1016/j.pain.2011.07.005.
• Fink RM, Hjort E, Wenger B, Cook PF, Cunningham M, Orf A, Pare W, Zwink J. The impact of dry versus moist heat on peripheral IV catheter insertion in a hematology-oncology outpatient population. Oncol Nurs Forum. 2009 Jul;36(4):E198-204. doi: 10.1188/09.ONF.E198-E204.
• Lima-Oliveira G, Lippi G, Salvagno GL, Montagnana M, Picheth G, Guidi GC. Impact of the phlebotomy training based on CLSI/NCCLS H03-a6 - procedures for the collection of diagnostic blood specimens by venipuncture. Biochem Med (Zagreb). 2012;22(3):342-51.
• Shah JS, Soon PS, Marsh DJ. Comparison of Methodologies to Detect Low Levels of Hemolysis in Serum for Accurate Assessment of Serum microRNAs. PLoS One. 2016 Apr 7;11(4):e0153200. doi: 10.1371/journal.pone.0153200. eCollection 2016.
• Yamagami Y, Tomita K, Tsujimoto T, Inoue T. Tourniquet application after local forearm warming to improve venodilation for peripheral intravenous cannulation in young and middle-aged adults: A single-blind prospective randomized controlled trial. Int J Nurs Stud. 2017 Jul;72:1-7. doi: 10.1016/j.ijnurstu.2017.03.009. Epub 2017 Mar 27.

• Responsible Party: Universidad Complutense de Madrid
• ClinicalTrials.gov Identifier: NCT04027218
• Other Study ID Numbers: 3113
• First Posted: Jul 19, 2019
• Last Update Posted: Nov 13, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Universidad Complutense de Madrid: venipuncture; hemolysis; heat; pressure; safety
• Additional relevant MeSH terms: Hemolysis

Study Results

Participant Flow

Pre-assignment Detail	63 individuals signed informed consent form, but one of them did not meet all the inclusion criteria. Then 62 participants were included in the study.

Arm/Group Title	Current Clinical Practice First, Washout, Then Dry Heat	Current Clinical Practice First, Washout, Then High Pressure	Current Clinical Practice First, Washout, Then Combination	Dry Heat First, Washout, Then Current Clinical Practice	High Pressure First, Washout, Then Current Clinical Practice	Combination First, Washout, Then Current Clinical Practice
Arm/Group Description	First (day 1): The standardized and approved Clinical and Laboratory Standards Institute (CLSI) GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital. Washout (1 week) Second (1 day): Dry heat: The application is made with two sacks of carob seeds during 7 minutes. The sacks are placed on antebrachial anatomical zone, together, and previously heated in the microwave for 0.30 seconds at 850 W of power.	First (day 1):The standardized and approved CLSI GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital. Washout (1 week) Second (1 day): High pressure: It will be carried out with the use of the manual aneroid sphygmomanometer fixed at 100 millimeters of mercury. Brand (QUIRUMED) with European Conformity (CE) marking 0197. A pressure lower than the systolic blood pressure, and in each subject will be monitored the radial pulse.	First (day 1): The standardized and approved CLSI GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital. Washout (1 week) Second (1 day): Combination of dry heat and high pressure: as described in dry heat application, and after 7 minutes, high pressure was applied as described for high pressure intervention.	First ( day 1): Dry heat: The application is made with two sacks of carob seeds during 7 minutes. The sacks are placed on antebrachial anatomical zone, together, and previously heated in the microwave for 0.30 seconds at 850 W of power. Washout (1 week) Second (day 1): The standardized and approved Clinical and Laboratory Standards Institute (CLSI) GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital.	First (day 1): High pressure: It will be carried out with the use of the manual aneroid sphygmomanometer fixed at 100 millimeters of mercury. Brand (QUIRUMED) with European Conformity (CE) marking 0197. A pressure lower than the systolic blood pressure, and in each subject will be monitored the radial pulse. Washout (1 week) Second (8 day 1):The standardized and approved CLSI GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital.	First (day 1): Combination of dry heat and high pressure: as described in dry heat application, and after 7 minutes, high pressure was applied as described for high pressure intervention. Washout (1 week) Second (day 1): The standardized and approved CLSI GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital.
Period Title: Overall Study
STARTED	10	11	9	11	10	11
COMPLETED	10	8	9	11	10	11
NOT COMPLETED	0	3	0	0	0	0

Baseline Characteristics

Arm/Group Title	Current Clinical Practice First, Washout, Then Dry Heat	Current Clinical Practice First, Washout, Then High Pressure	Current Clinical Practice First, Washout, Then Combination	Dry Heat First, Washout, Then Current Clinical Practice	High Pressure First, Washout, Then Current Clinical Practice	Combination First, Washout, Then Current Clinical Practice	Total
Arm/Group Description	First (day 1):The standardized and approved Clinical and Laboratory Standards Institute (CLSI) GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital. Washout (1 week) Second (1 day). Dry heat: The application is made with two sacks of carob seeds during 7 minutes. The sacks are placed on antebrachial anatomical zone, together, and previously heated in the microwave for 0.30 seconds at 850 W of power.	First (1 day): The standardized and approved CLSI GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital. Washout (1 week) . Second (1 day): High pressure: It will be carried out with the use of the manual aneroid sphygmomanometer fixed at 100 millimeters of mercury. Brand (QUIRUMED) with European Conformity (CE) marking 0197. A pressure lower than the systolic blood pressure, and in each subject will be monitored the radial pulse.	First (day 1):The standardized and approved CLSI GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital. Washout (1 week) Second (1 day): Combination of dry heat and high pressure: as described in dry heat application, and after 7 minutes, high pressure was applied as described for high pressure intervention.	First (1 day). Dry heat: The application is made with two sacks of carob seeds during 7 minutes. The sacks are placed on antebrachial anatomical zone, together, and previously heated in the microwave for 0.30 seconds at 850 W of power. Washout (1 week) Second (day 1):The standardized and approved Clinical and Laboratory Standards Institute (CLSI) GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital.	First (1 day): High pressure: It will be carried out with the use of the manual aneroid sphygmomanometer fixed at 100 millimeters of mercury. Brand (QUIRUMED) with European Conformity (CE) marking 0197. A pressure lower than the systolic blood pressure, and in each subject will be monitored the radial pulse. Washout (1 week) First (1 day): The standardized and approved CLSI GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital.	First (1 day): Combination of dry heat and high pressure: as described in dry heat application, and after 7 minutes, high pressure was applied as described for high pressure intervention. Washout (1 week) Second (day 1):The standardized and approved CLSI GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital.	Total of all reporting groups
Overall Participants	10	08	09	11	10	11	59
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25.33 (3.72)	30.00 (8.22)	26.78 (7.80)	27.36 (3.80)	26.30 (4.71)	25.45 (6.91)	26.72 (5.881)
Sex: Female, Male (Count of Participants)
Female	8 80%	4 50%	4 44.4%	9 81.8%	7 70%	7 63.6%	39 66.1%
Male	2 20%	4 50%	5 55.6%	2 18.2%	3 30%	4 36.4%	20 33.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	4 40%	3 37.5%	2 22.2%	4 36.4%	3 30%	5 45.5%	21 35.6%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 10%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.7%
White	5 50%	5 62.5%	7 77.8%	7 63.6%	7 70%	6 54.5%	37 62.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Grade of Venous International Assessment (VIA) scale (Count of Participants)
Grade II	2 20%	3 37.5%	4 44.4%	2 18.2%	1 10%	3 27.3%	15 25.4%
Grade III	2 20%	3 37.5%	4 44.4%	4 36.4%	1 10%	6 54.5%	20 33.9%
Grade IV	6 60%	2 25%	1 11.1%	4 36.4%	8 80%	2 18.2%	23 39%
Grade V	0 0%	0 0%	0 0%	1 9.1%	0 0%	0 0%	1 1.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Successful Venous Catheterization at the First Attempt
Description	Number of participants with successful venous catheterization at the first attempt (effectiveness)
Time Frame	From 1-5 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dry Heat	High Pressure	Combination	Current Clinical Practice
Arm/Group Description	Dry heat: The application is made with two sacks of carob seeds during 7 minutes. The sacks are placed on antebrachial anatomical zone, together, and previously heated in the microwave for 0.30 seconds at 850 W of power.	High pressure: It will be carried out with the use of the manual aneroid sphygmomanometer fixed at 100 millimeters of mercury. Brand (QUIRUMED) with European Conformity (CE) marking 0197. A pressure lower than the systolic blood pressure, and in each subject will be monitored the radial pulse.	Combination of dry heat and high pressure: The application is made with two sacks of carob seeds during 7 minutes, then application of high pressure as described is carried out.	The standardized and approved Clinical and Laboratory Standards Institute (CLSI) GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital.
Measure Participants	21	18	20	59
Count of Participants [Participants]	21 210%	18 225%	19 211.1%	28 254.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dry Heat, Current Clinical Practice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	McNemar
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.57
	Confidence Interval	(2-Sided) 95%; 2.34 to 2.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High Pressure, Current Clinical Practice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	McNemar
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.92
	Confidence Interval	(2-Sided) 95%; 1.70 to 2.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combination, Current Clinical Practice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	McNemar
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.90
	Confidence Interval	(2-Sided) 95%; 1.87 to 1.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of the Grade of Venous International Assessment (VIA) Scale After Application of Intervention
Description	Vein perception in VIA scale was considered as the self-reported visual observation or palpation of a venous pathway. Subjects were graded using the current clinical practice vein stagnation with an elastic compressor application (Unidix®). Five grades considering the numbers of points of optimal puncture visible and tangible, in one of the dorsal veins of the hand, forearm cephalic and/or basilic. Grade I: At least six. Grade II: At least four. Grade III: At least three. Grade IV: At least one. Grade V: None. Therefore, the best grade is I, and the worst grade is V. Higher scores mean a worse outcome.
Time Frame	up to ten minutes after application of intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dry Heat	High Pressure	Combination	Current Clinical Practice
Arm/Group Description	Dry heat: The application is made with two sacks of carob seeds during 7 minutes. The sacks are placed on antebrachial anatomical zone, together, and previously heated in the microwave for 0.30 seconds at 850 W of power.	High pressure: It will be carried out with the use of the manual aneroid sphygmomanometer fixed at 100 millimeters of mercury. Brand (QUIRUMED) with European Conformity (CE) marking 0197. A pressure lower than the systolic blood pressure, and in each subject will be monitored the radial pulse.	Combination of dry heat and high pressure: The application is made with two sacks of carob seeds during 7 minutes, then application of high pressure as described is carried out.	The standardized and approved Clinical and Laboratory Standards Institute (CLSI) GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital.
Measure Participants	21	18	20	59
Median (Full Range) [units on a scale]	2	2	1	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dry Heat, Current Clinical Practice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.000
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-4.179
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High Pressure, Current Clinical Practice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.000
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-3.619
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combination, Current Clinical Practice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.000
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-4.099
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of the Grade in Visual Analogue Scale (VAS) for Pain After Intervention
Description	Visual Analogue Scale (VAS) in pain was measured by integer number. Pain was self-expressed by participants, in a range from 0 to 10. 10: was considered the worst pain experienced 0: no pain perceived. The entire range was 0, 1, 2, 3, 4, 5 , 6, 7, 8, 9, 10. Therefore, higher scores mean a worse outcome.
Time Frame	up to 2 hours after application of intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dry Heat	High Pressure	Combination	Current Clinical Practice
Arm/Group Description	Dry heat: The application is made with two sacks of carob seeds during 7 minutes. The sacks are placed on antebrachial anatomical zone, together, and previously heated in the microwave for 0.30 seconds at 850 W of power.	High pressure: It will be carried out with the use of the manual aneroid sphygmomanometer fixed at 100 millimeters of mercury. Brand (QUIRUMED) with European Conformity (CE) marking 0197. A pressure lower than the systolic blood pressure, and in each subject will be monitored the radial pulse.	Combination of dry heat and high pressure: The application is made with two sacks of carob seeds during 7 minutes, then application of high pressure as described is carried out.	The standardized and approved Clinical and Laboratory Standards Institute (CLSI) GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital.
Measure Participants	21	18	20	59
Mean (Full Range) [units on a scale]	3	2	2.5	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dry Heat, Current Clinical Practice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.863
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-1.073
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value corresponds with the number of negative changes, which implies participants with decrease in VAS score.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High Pressure, Current Clinical Practice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.205
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-1.267
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value corresponds with the number of negative changes, which implies participants with decrease in VAS score.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combination, Current Clinical Practice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.391
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-0.858
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value corresponds with the number of negative changes, which implies participants with decrease in VAS score.

4. Secondary Outcome

Title	Number of Participants in Each Type of Skin Standardized According to Fitzpatrick Scale
Description	Number of participants in each type of skin standardized according to Fitzpatrick scale. Fitzpatrick scale is the UNABBREVIATED scale that indicates different types of skin described as "phototypes". The individuals were graded clinically by sel-expressed by participants in the area of the forearm not exposed to the sun. In a range of six phototypes, where phototype I corresponds with the minimum and phototype VI the maximum. Phototype I: Ivory white, burns easily, never tans. Phototype II: White, burns easily, tans minimally with difficulty. Phototype III: White, burns moderately, tans moderately and uniformly Phototype IV: Beige-olive, lightly tanned, burns minimally, tans moderately and easily. Phototype V: Rarely burns, tans profusely. Phototype VI: Dark brown or black, never burns, tans profusely. Phototype I was considered more risky outcome for expected adverse events in skin. None was considered better or worse outcome.
Time Frame	up to 2 hours after application of intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dry Heat	High Pressure	Combination	Current Clinical Practice
Arm/Group Description	Dry heat: The application is made with two sacks of carob seeds during 7 minutes. The sacks are placed on antebrachial anatomical zone, together, and previously heated in the microwave for 0.30 seconds at 850 W of power.	High pressure: It will be carried out with the use of the manual aneroid sphygmomanometer fixed at 100 millimeters of mercury. Brand (QUIRUMED) with European Conformity (CE) marking 0197. A pressure lower than the systolic blood pressure, and in each subject will be monitored the radial pulse.	Combination of dry heat and high pressure: The application is made with two sacks of carob seeds during 7 minutes, then application of high pressure as described is carried out.	The standardized and approved Clinical and Laboratory Standards Institute (CLSI) GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital.
Measure Participants	21	18	20	59
Phototype I	1 10%	1 12.5%	0 0%	2 18.2%
Phototype II	2 20%	2 25%	1 11.1%	5 45.5%
Phototype III	9 90%	6 75%	8 88.9%	23 209.1%
Phototype IV	7 70%	8 100%	8 88.9%	23 209.1%
Phototype V	1 10%	1 12.5%	3 33.3%	5 45.5%
Phototype VI	1 10%	0 0%	0 0%	1 9.1%

5. Secondary Outcome

Title	Level of Hemolysis in Absorbance Units
Description	Detection level of absorbance values of hemolysis in plasma samples. The units of absorbance are dimensionless. The hemolysis in plasma is analyzed by spectrophotometry method, using a NanoDrop® 2000 Spectrophotometer device (Thermo Fisher Scientific Inc., Wilmington, United States of America). The following equation was used to correct lipemia: (A414-A385) +0.16xA385. Additionally, a baseline correction factor at 750 nanometer wavelength was applied. Therefore, absorbance were measured at 414 nanometer, 385 nanometer and 750 nanometer. Higher values represent a worse outcome: higher value mean higher hemolysis in a blood sample. Therefore, lower values, near to zero are better outcomes that mean low hemolysis in blood sample.
Time Frame	up to 9 days after first intervention completion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dry Heat	High Pressure	Combination	Current Clinical Practice
Arm/Group Description	Dry heat: The application is made with two sacks of carob seeds during 7 minutes. The sacks are placed on antebrachial anatomical zone, together, and previously heated in the microwave for 0.30 seconds at 850 W of power.	High pressure: It will be carried out with the use of the manual aneroid sphygmomanometer fixed at 100 millimeters of mercury. Brand (QUIRUMED) with European Conformity (CE) marking 0197. A pressure lower than the systolic blood pressure, and in each subject will be monitored the radial pulse.	Combination of dry heat and high pressure: The application is made with two sacks of carob seeds during 7 minutes, then application of high pressure as described is carried out.	The standardized and approved Clinical and Laboratory Standards Institute (CLSI) GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital.
Measure Participants	21	18	20	59
Median (Full Range) [Absorbance units]	0.08	0.08	0.14	0.07

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dry Heat, Current Clinical Practice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.502
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-0.672
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value corresponds with the absorbance comparing hemolysis in blood samples performed by clinical practice against to the corresponding intervention.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High Pressure, Current Clinical Practice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.744
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-0.327
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value corresponds with the absorbance comparing hemolysis in blood samples performed by clinical practice against to the corresponding intervention.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combination, Current Clinical Practice
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.059
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-1.885
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimated value corresponds with the absorbance comparing hemolysis in blood samples performed by clinical practice against to the corresponding intervention.

6. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Number of adverse events by visual inspection.
Time Frame	During the study completion,. an average of 30 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dry Heat	High Pressure	Combination	Current Clinical Practice
Arm/Group Description	Dry heat: The application is made with two sacks of carob seeds during 7 minutes. The sacks are placed on antebrachial anatomical zone, together, and previously heated in the microwave for 0.30 seconds at 850 W of power.	High pressure: It will be carried out with the use of the manual aneroid sphygmomanometer fixed at 100 millimeters of mercury. Brand (QUIRUMED) with European Conformity (CE) marking 0197. A pressure lower than the systolic blood pressure, and in each subject will be monitored the radial pulse.	Combination of dry heat and high pressure: The application is made with two sacks of carob seeds during 7 minutes, then application of high pressure as described is carried out.	The standardized and approved Clinical and Laboratory Standards Institute (CLSI) GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital.
Measure Participants	21	18	20	59
Count of Participants [Participants]	7 70%	1 12.5%	6 66.7%	0 0%

Adverse Events

Time Frame	Adverse events were collected during the study completion, an average of 30 days.
Adverse Event Reporting Description	Because in this clinical trial using dry heat and high pressure were only expected local erythema and transient paresthesia as adverse events. The treatment for those adverse events, if applicable, were not consider a requirement of medical or surgical intervention. A supervision (for local erythema) and release the pressure (for transient paresthesia) were considered sufficient as treatment.
Arm/Group Title	Dry Heat		High Pressure		Combination		Current Clinical Practice
Arm/Group Description	Dry heat: The application is made with two sacks of carob seeds during 7 minutes. The sacks are placed on antebrachial anatomical zone, together, and previously heated in the microwave for 0.30 seconds at 850 W of power.		High pressure: It will be carried out with the use of the manual aneroid sphygmomanometer fixed at 100 millimeters of mercury. Brand (QUIRUMED) with European Conformity (CE) marking 0197. A pressure lower than the systolic blood pressure, and in each subject will be monitored the radial pulse.		Combination of dry heat and high pressure: The application is made with two sacks of carob seeds during 7 minutes, then application of high pressure as described is carried out.		The standardized and approved Clinical and Laboratory Standards Institute (CLSI) GP41-A6 venipuncture guide has been established for clinical current practice so far. According to vein cannulation procedure CLSI GP41-A6, an elastic compressor will be applied (Synthetic rubber-latex compressor tape, UNIDIX®, Madrid, Spain) provided by the hospital.
All Cause Mortality
	Dry Heat		High Pressure		Combination		Current Clinical Practice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/18 (0%)		0/20 (0%)		0/59 (0%)
Serious Adverse Events
	Dry Heat		High Pressure		Combination		Current Clinical Practice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/18 (0%)		0/20 (0%)		0/59 (0%)
Other (Not Including Serious) Adverse Events
	Dry Heat		High Pressure		Combination		Current Clinical Practice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/21 (33.3%)		1/21 (4.8%)		6/20 (30%)		0/59 (0%)
Blood and lymphatic system disorders
Local erythema	7/21 (33.3%)	7	0/21 (0%)	0	6/20 (30%)	6	0/59 (0%)	0
Nervous system disorders
Transient paresthesia	0/21 (0%)	0	1/21 (4.8%)	1	0/20 (0%)	0	0/59 (0%)	0

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.