Effectiveness Novel Tissue Sealant, Prevention Prolonged Air Leak (PAL) After Lung Resection

• Sponsor: Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León (Other)
• Overall Status: Completed
• CT.gov ID: NCT02491671
• Collaborator: Instituto de Investigación Biomédica de Salamanca (Other), Baxter Healthcare Corporation (Industry)
• Enrollment: 260
• Locations: 6
• Arms: 2
• Actual Duration (Months): 43.2
• Patients Per Site: 43.3
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The effectiveness of tissue sealants to prevent Prolonged Air Leak (PAL) after lung resection procedures remains unproved. The investigators hypothesize that one of the main reasons for that is the heterogeneity of previously studied populations. Since currently the risk of postoperative PAL can be scored with a reasonable accuracy, the aim of this research is to investigate the effect of routine application of a novel tissue sealant in patients selected on the basis of a high risk of PAL estimated before surgery.

Condition or Disease	Intervention/Treatment	Phase
Prolonged Air Leak; Lung Resection	Device: Hemopatch; Procedure: standard preventive measures	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 260 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Prospective, Multicenter, Open-Label, Randomized, Phase III Clinical Trial of Prevention of Prolonged Air Leak After Lung Resection in High-risk Patients, Applying HEMOPATCH®
• Actual Study Start Date: Nov 24, 2015
• Actual Primary Completion Date: Jun 30, 2019
• Actual Study Completion Date: Jun 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental group Experimental group: At the end of lung resection, lung sutures and 1.5 cm of lung parenchyma on each side will be covered by Hemopatch. No additional measures for preventing air leak will be indicated. In the case of massive air leak in spite of the use of Hemopatch, each surgeon will decide on the indication of additional sutures of tissue plasties. These cases will be accounted for failures on an intention to treat basis.	Device: Hemopatch; Procedure: standard preventive measures
Other: Control group Control group: The standard preventive measures will be followed in each center, including reinforcement of sutures, pleural tents, suturing pericardial or subcutaneous fat	Procedure: standard preventive measures

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Prolonged Air Leak (PAL) [From day of surgery to the fifth postoperative day]

   Prevalence of Prolonged Air Leak (PAL) measured as binary variable (YES/NO) and recorded, from day of surgery to the fifth postoperative day, in the study questionnaire. The occurrence of the outcome will be recorded if air leak exists 5 days or more after surgery

Secondary Outcome Measures

1. Duration of Air Leaks [Check everyday from day of surgery up to 38 days post-operative at maximum]

   Measured as continuous variable (days) and recorded, from day of surgery to the day of withdraw the chest tube. (standardized criteria for pulling out chest drainage/s will be agreed among investigators)

2. Number of Participants With at Least One Chest Tube Reinsertion [From day of surgery up to 30 days thereafter]

   Rate of patients needing postoperative reinsertion of chest drainages due to symptomatic pneumothorax. Following daily during hospital stay and pone follow-up until 30th day post-operative.

3. Number of Participants With One or More Readmission [30 days post-operative]

   Rate of readmissions due to relapsing pneumothorax (follow-up 30 days)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Scheduled anatomical lung resection indicated for any non-infectious disease (excluding Pneumonectomy)

• Patients classified in class D according estimated risk of PAL

• Age between 18 and 80 years

Exclusion Criteria:

• Those patients that according to Investigator assessment are not going to tolerate the procedure

• Clinical and anesthetic criteria that contraindicate surgery

• Severe uncontrolled illness

• Pregnancy

• Patients that are under Investigational New Drug treatment or have participated in study with a investigational drug (authorized or not) in 30 days before randomization.

• Lack of Informed Consent or patient refusal

• Postsurgery mechanical ventilation or repeated surgery in follow-up month.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario Marqués de Valdecilla de Santander	Santander	Cantabria	Spain	39008
2	Hospital Clinic	Barcelona		Spain	08036
3	Hospital Universitario Ramón y Cajal de Madrid	Madrid		Spain	28034
4	Hospital Clínico San Carlos	Madrid		Spain	28040
5	Hospital Universitario de Salamanca (CAUSA)	Salamanca		Spain	37007
6	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013

Sponsors and Collaborators

• Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
• Instituto de Investigación Biomédica de Salamanca
• Baxter Healthcare Corporation

Investigators

• Study Director: Gonzalo Varela, MD PhD FETCS, IBSAL-Instituto de Investigación Biomédica de Salamanca

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 17, 2017
• Informed Consent Form - Mar 3, 2015

More Information

Publications

None provided.

• Responsible Party: Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
• ClinicalTrials.gov Identifier: NCT02491671
• Other Study ID Numbers: HEMOPATCH/FAP/2014
• First Posted: Jul 8, 2015
• Last Update Posted: Aug 9, 2021
• Last Verified: Aug 1, 2021

• Keywords provided by Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León: Prevention PAL Prolonged Air Leak (PAL); Lung Resection; Thoracic Surgery; Post-operative Thoracic Air Leak

Study Results

Participant Flow

Arm/Group Title	Experimental Group	Control Group
Arm/Group Description	Experimental group: At the end of lung resection, lung sutures and 1.5 cm of lung parenchyma on each side will be covered by Hemopatch. No additional measures for preventing air leak will be indicated. In the case of massive air leak in spite of the use of Hemopatch, each surgeon will decide on the indication of additional sutures of tissue plasties. These cases will be accounted for failures on an intention to treat basis. Hemopatch standard preventive measures	Control group: The standard preventive measures will be followed in each center, including reinforcement of sutures, pleural tents, suturing pericardial or subcutaneous fat standard preventive measures
Period Title: Overall Study
STARTED	129	131
COMPLETED	118	118
NOT COMPLETED	11	13

Baseline Characteristics

Arm/Group Title	Experimental Group	Control Group	Total
Arm/Group Description	Experimental group: At the end of lung resection, lung sutures and 1.5 cm of lung parenchyma on each side will be covered by Hemopatch. No additional measures for preventing air leak will be indicated. In the case of massive air leak in spite of the use of Hemopatch, each surgeon will decide on the indication of additional sutures of tissue plasties. These cases will be accounted for failures on an intention to treat basis. Hemopatch standard preventive measures	Control group: The standard preventive measures will be followed in each center, including reinforcement of sutures, pleural tents, suturing pericardial or subcutaneous fat standard preventive measures	Total of all reporting groups
Overall Participants	118	118	236
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	70.77	70.76	70.77
Sex: Female, Male (Count of Participants)
Female	25 21.2%	27 22.9%	52 22%
Male	93 78.8%	91 77.1%	184 78%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Spain	118 100%	118 100%	236 100%
Body Mass Index (kg/m^2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg/m^2]	24.5	24.27	24.4
American Society of Anesthesiologists (ASA) classification (Count of Participants)
ASA 2	54 45.8%	51 43.2%	105 44.5%
ASA 3	62 52.5%	65 55.1%	127 53.8%
ASA 4	2 1.7%	2 1.7%	4 1.7%
Type of Surgery (Count of Participants)
Segmentectomy	7 5.9%	4 3.4%	11 4.7%
Lobectomy	106 89.8%	107 90.7%	213 90.3%
Bilobectomy	5 4.2%	7 5.9%	12 5.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Prolonged Air Leak (PAL)
Description	Prevalence of Prolonged Air Leak (PAL) measured as binary variable (YES/NO) and recorded, from day of surgery to the fifth postoperative day, in the study questionnaire. The occurrence of the outcome will be recorded if air leak exists 5 days or more after surgery
Time Frame	From day of surgery to the fifth postoperative day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Group	Control Group
Arm/Group Description	Experimental group: At the end of lung resection, lung sutures and 1.5 cm of lung parenchyma on each side will be covered by Hemopatch. No additional measures for preventing air leak will be indicated. In the case of massive air leak in spite of the use of Hemopatch, each surgeon will decide on the indication of additional sutures of tissue plasties. These cases will be accounted for failures on an intention to treat basis. Hemopatch standard preventive measures	Control group: The standard preventive measures will be followed in each center, including reinforcement of sutures, pleural tents, suturing pericardial or subcutaneous fat standard preventive measures
Measure Participants	118	118
Count of Participants [Participants]	33 28%	24 20.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental Group, Control Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.171
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.219
	Confidence Interval	(2-Sided) 95%; 0.891 to 1.583
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Duration of Air Leaks
Description	Measured as continuous variable (days) and recorded, from day of surgery to the day of withdraw the chest tube. (standardized criteria for pulling out chest drainage/s will be agreed among investigators)
Time Frame	Check everyday from day of surgery up to 38 days post-operative at maximum

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Group	Control Group
Arm/Group Description	Experimental group: At the end of lung resection, lung sutures and 1.5 cm of lung parenchyma on each side will be covered by Hemopatch. No additional measures for preventing air leak will be indicated. In the case of massive air leak in spite of the use of Hemopatch, each surgeon will decide on the indication of additional sutures of tissue plasties. These cases will be accounted for failures on an intention to treat basis. Hemopatch standard preventive measures	Control group: The standard preventive measures will be followed in each center, including reinforcement of sutures, pleural tents, suturing pericardial or subcutaneous fat standard preventive measures
Measure Participants	118	118
Mean (Full Range) [days]	1	1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental Group, Control Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	z
	Estimated Value	0.288
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Wilcoxon rank-sum (Mann-Whitney) test Unadjusted variance 274999.00 Adjustment for ties --21069.78 Adjusted variance 253929.22 z = 0.288; Prob > |z| = 0.7735

3. Secondary Outcome

Title	Number of Participants With at Least One Chest Tube Reinsertion
Description	Rate of patients needing postoperative reinsertion of chest drainages due to symptomatic pneumothorax. Following daily during hospital stay and pone follow-up until 30th day post-operative.
Time Frame	From day of surgery up to 30 days thereafter

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Group	Control Group
Arm/Group Description	Experimental group: At the end of lung resection, lung sutures and 1.5 cm of lung parenchyma on each side will be covered by Hemopatch. No additional measures for preventing air leak will be indicated. In the case of massive air leak in spite of the use of Hemopatch, each surgeon will decide on the indication of additional sutures of tissue plasties. These cases will be accounted for failures on an intention to treat basis. Hemopatch standard preventive measures	Control group: The standard preventive measures will be followed in each center, including reinforcement of sutures, pleural tents, suturing pericardial or subcutaneous fat standard preventive measures
Measure Participants	118	118
Count of Participants [Participants]	3 2.5%	6 5.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental Group, Control Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0 .307
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.351
	Confidence Interval	(2-Sided) 95%; 0.657 to 1.879
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants With One or More Readmission
Description	Rate of readmissions due to relapsing pneumothorax (follow-up 30 days)
Time Frame	30 days post-operative

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Group	Control Group
Arm/Group Description	Experimental group: At the end of lung resection, lung sutures and 1.5 cm of lung parenchyma on each side will be covered by Hemopatch. No additional measures for preventing air leak will be indicated. In the case of massive air leak in spite of the use of Hemopatch, each surgeon will decide on the indication of additional sutures of tissue plasties. These cases will be accounted for failures on an intention to treat basis. Hemopatch standard preventive measures	Control group: The standard preventive measures will be followed in each center, including reinforcement of sutures, pleural tents, suturing pericardial or subcutaneous fat standard preventive measures
Measure Participants	118	118
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	Through study completion, a total of up to 3 months.
Arm/Group Title	Experimental Group		Control Group
Arm/Group Description	Experimental group: At the end of lung resection, lung sutures and 1.5 cm of lung parenchyma on each side will be covered by Hemopatch. No additional measures for preventing air leak will be indicated. In the case of massive air leak in spite of the use of Hemopatch, each surgeon will decide on the indication of additional sutures of tissue plasties. These cases will be accounted for failures on an intention to treat basis. Hemopatch standard preventive measures		Control group: The standard preventive measures will be followed in each center, including reinforcement of sutures, pleural tents, suturing pericardial or subcutaneous fat standard preventive measures
All Cause Mortality
	Experimental Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/118 (0%)		2/118 (1.7%)
Serious Adverse Events
	Experimental Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/118 (2.5%)		7/118 (5.9%)
Injury, poisoning and procedural complications
Reoperation for bleeding	1/118 (0.8%)	1	3/118 (2.5%)	3
Respiratory, thoracic and mediastinal disorders
Pulmonary. Mechanical ventilation	2/118 (1.7%)	2	4/118 (3.4%)	4
Other (Not Including Serious) Adverse Events
	Experimental Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/118 (0%)		0/118 (0%)

Limitations/Caveats

Only the population in which a very high rate of PAL is expected was enrolled. There was no stratification by lung function or type of lung resection.

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.