Erythropoietin to Enhance Recovery of Erectile Function in Men Following Radical Prostatectomy

Prostate Cancer Clinical Trial

— ERECT  

Official title:

Erythropoietin to Enhance Recovery of Erectile Function in Men Following Radical Prostatectomy: a Prospective Randomized Controlled Trial (ERECT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00737893
• Other study ID #: IRB00048594
• Secondary ID: ERECT, EPO
• Status: Completed
• Phase: Phase 2
• Start date: July 1, 2017
• Est. completion date: December 31, 2019

Study information

• Verified date: July 2020
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research study aims to explore the effectiveness of human erythropoietin versus placebo in promoting the recovery of erectile function in patients undergoing bilateral nerve-sparing radical retropubic prostatectomy for clinically localized prostate cancer. Pre-clinical studies have shown erythropoietin potently promoted recovery of erectile function in rats and humans have similar receptors on penile tissues and the periprostatic neurovascular bundles. A clinical non-randomized study conducted in men undergoing radical prostatectomy demonstrated a benefit to recovery of erectile function. Therefore, the hypothesis is that erythropoietin offers nerve protection in men undergoing nerve-sparing radical prostatectomy and results in a reduced degree of erectile dysfunction and also an improved rate of erection recovery following surgery.

Description:

This study will evaluate the effectiveness of erythropoietin versus placebo in the recovery of erectile function in patients undergoing bilateral nerve-sparing radical prostatectomy for prostate cancer. Recent laboratory findings in rat models and on human urogenital tissues suggest that erythropoietin may play a role in protection of the cavernous nerves during surgery. Some degree of nerve trauma occurs during bilateral nerve-sparing radical prostatectomy, but for most it is temporary. Erythropoietin will be studied as an investigational drug for enhancement of erectile function postoperatively in a prospective, randomized study. Erythropoietin has been used in many men undergoing open radical prostatectomy in the past according to FDA indications for preparation for noncardiac, nonvascular surgery with a high risk of blood loss. Evidence also suggests it is safe with no demonstration of increased risk of venous thromboembolism (blood clots) or cardiac events for men with prostate cancer undergoing radical prostatectomy. The length of the study is 12 months and involves receiving a dose of study drug or placebo on the day before surgery, the day of surgery, and the day following surgery. The dose is given by subcutaneous injection. The study will also require the completion of questionnaires which will be completed online every three months until study completion (at 3, 6, 9, and 12 months) to assess outcomes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patient eligibility consists of men 40 to 65 years of age
• Localized prostate cancer
• clinical stage T2a or lower
• Gleason grade of 3+4 or 3+3
• prostate specific antigen (PSA) < 10
• Scheduled to undergo curative prostatectomy applying bilateral nerve-sparing procedure, with intact pre-surgical erectile function
• International Index of Erectile Function-5 (IIEF-5) score of 22-25.
• The patient has a sexual partner, of at least 6 months.
• The patient's pre-surgical hematocrit is = 48.
• The patient is willing to attempt intercourse at least 5 times per month following recovery from surgery.

Exclusion Criteria:

• The patient has known penile deformity or a history of Peyronie's disease.
• The patient has planned pre or post operative androgen therapy.
• The patient has planned pre or post operative radiation therapy.
• The patient is on anticoagulation therapy.
• The patient has a history of sickle cell anemia.
• The patient has a history of high or low blood pressure that is not controlled.
• The patient is taking medications called "nitrates"
• The patient has a history of heart problems such as angina, heart failure, irregular heartbeats, or myocardial infarction
• The patient has a history of history of drug or alcohol abuse.
• The patient currently smokes or has a 20 pack/year history of cigarette smoking.
• The patient has a history of acute or chronic depression
• The patient has a history liver problems, or kidney problems.
• The patient has a history of retinitis pigmentosa or severe vision loss, including a condition called NAION, Nonarteritic Anterior Ischemic Optic Neuropathy.
• The patient has a history of spinal trauma or surgery to the brain or spinal cord.
• The patient has contraindications to the use of phosphodiesterase type 5 (PDE 5) inhibitors.
• Patient is currently participating in another clinical investigation that would serve as a contraindication to administering erythropoietin.

Related Conditions & MeSH terms

• Erectile Dysfunction
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Placebo
Saline injection (solution prepared by research pharmacy) subcutaneously given the day before surgery, day of surgery, and the day after surgery.
• Erythropoietin (EPO)
Erythropoietin (EPO)-induced Protein 29, Human; 20,000 units subcutaneously given the day before surgery, day of surgery, and the day after surgery.

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

References & Publications (5)

Allaf ME, Hoke A, Burnett AL. Erythropoietin promotes the recovery of erectile function following cavernous nerve injury. J Urol. 2005 Nov;174(5):2060-4. — View Citation

Burnett AL, Allaf ME, Bivalacqua TJ. Erythropoietin promotes erection recovery after nerve-sparing radical retropubic prostatectomy: a retrospective analysis. J Sex Med. 2008 Oct;5(10):2392-8. doi: 10.1111/j.1743-6109.2008.00980.x. Epub 2008 Sep 5. — View Citation

Liu T, Allaf ME, Lagoda G, Burnett AL. Erythropoietin receptor expression in the human urogenital tract: immunolocalization in the prostate, neurovascular bundle and penis. BJU Int. 2007 Nov;100(5):1103-6. Epub 2007 Sep 14. — View Citation

Patel HD, Allaf ME. Erythropoietin to Enhance Recovery of Erectile Function in Men Following Radical Prostatectomy: The ERECT Trial. Eur Urol Focus. 2019 Jul;5(4):698-699. doi: 10.1016/j.euf.2018.01.002. Epub 2018 Jan 17. — View Citation

Patel HD, Schwen ZR, Campbell JD, Gorin MA, Partin AW, Burnett AL, Allaf ME. Effect of Erythropoietin on Erectile Function after Radical Prostatectomy: The ERECT Randomized Clinical Trial. J Urol. 2021 Feb 3:101097JU0000000000001586. doi: 10.1097/JU.00000 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Erectile Function as Assessed by the International Index of Erectile Function (IIEF) Questionnaire Erectile Function Domain	Survey measuring erectile function using the IIEF (erectile function domain only) with overall score ranging from 0 to 30 where higher scores represent better erectile function.	At 6 months post-surgery
Secondary	Erectile Function as Assessed by the IIEF Questionnaire Erectile Function Domain	Survey measuring erectile function using the IIEF (erectile function domain only) with overall score ranging from 0 to 30 where higher scores represent better erectile function.	At 3 months post-surgery
Secondary	Erectile Function as Assessed by the IIEF Questionnaire Erectile Function Domain	Survey measuring erectile function using the IIEF (erectile function domain only) with overall score ranging from 0 to 30 where higher scores represent better erectile function.	At 9 months post-surgery
Secondary	Erectile Function as Assessed by the IIEF Questionnaire Erectile Function Domain	Survey measuring erectile function using the IIEF (erectile function domain only) with overall score ranging from 0 to 30 where higher scores represent better erectile function.	At 12 months post-surgery
Secondary	Patient Score on the Overall IIEF Questionnaire	Survey measuring erectile function using the IIEF (overall questionnaire) with overall score ranging from 0 to 75 where higher scores represent better erectile function.	At 3 months post-surgery
Secondary	Patient Score on the Overall IIEF Questionnaire	Survey measuring erectile function using the IIEF (overall questionnaire) with overall score ranging from 0 to 75 where higher scores represent better erectile function.	At 6 months post-surgery
Secondary	Patient Score on the Overall IIEF Questionnaire	Survey measuring erectile function using the IIEF (overall questionnaire) with overall score ranging from 0 to 75 where higher scores represent better erectile function.	At 9 months post-surgery
Secondary	Patient Score on the Overall IIEF Questionnaire	Survey measuring erectile function using the IIEF (overall questionnaire) with overall score ranging from 0 to 75 where higher scores represent better erectile function.	At 12 months post-surgery
Secondary	Patient Score on Health-related Quality of Life Questionnaires (SF-12 MCS)	Mental health composite score (MCS) component of the 12-Item Short Form Survey Instrument (SF-12) measured on a normalized scale with mean 50 and standard deviation 10 in the United States population. Higher scores represent a higher level of mental health.	At 3 months post-surgery
Secondary	Patient Score on Health-related Quality of Life Questionnaires (SF-12 MCS)	Mental health composite score (MCS) component of the 12-Item Short Form Survey Instrument (SF-12) measured on a normalized scale with mean 50 and standard deviation 10 in the United States population. Higher scores represent a higher level of mental health.	At 6 months post-surgery
Secondary	Patient Score on Health-related Quality of Life Questionnaires (SF-12 MCS)	Mental health composite score (MCS) component of the 12-Item Short Form Survey Instrument (SF-12) measured on a normalized scale with mean 50 and standard deviation 10 in the United States population. Higher scores represent a higher level of mental health.	At 9 months post-surgery
Secondary	Patient Score on Health-related Quality of Life Questionnaires (SF-12 MCS)	Mental health composite score (MCS) component of the 12-Item Short Form Survey Instrument (SF-12) measured on a normalized scale with mean 50 and standard deviation 10 in the United States population. Higher scores represent a higher level of mental health.	At 12 months post-surgery
Secondary	Patient Score on the Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain	Sexual health domain score of the EPIC survey measuring health-related quality of life with higher scores representing better sexual function on a scale of 0 to 100.	At 3 months post-surgery
Secondary	Patient Score on the Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain	Sexual health domain score of the EPIC survey measuring health-related quality of life with higher scores representing better sexual function on a scale of 0 to 100.	At 6 months post-surgery
Secondary	Patient Score on the Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain	Sexual health domain score of the EPIC survey measuring health-related quality of life with higher scores representing better sexual function on a scale of 0 to 100.	At 9 months post-surgery
Secondary	Patient Score on the Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain	Sexual health domain score of the EPIC survey measuring health-related quality of life with higher scores representing better sexual function on a scale of 0 to 100.	At 12 months post-surgery
Secondary	Patient Score on the Quality of Erection Questionnaire (QEQ)	Survey measuring quality of erections using the QEQ with an overall score range of 0 to 100 where higher scores represent better erection quality.	At 3 months post-surgery
Secondary	Patient Score on the Quality of Erection Questionnaire (QEQ)	Survey measuring quality of erections using the QEQ with an overall score range of 0 to 100 where higher scores represent better erection quality.	At 6 months post-surgery
Secondary	Patient Score on the Quality of Erection Questionnaire (QEQ)	Survey measuring quality of erections using the QEQ with an overall score range of 0 to 100 where higher scores represent better erection quality.	At 9 months post-surgery
Secondary	Patient Score on the Quality of Erection Questionnaire (QEQ)	Survey measuring quality of erections using the QEQ with an overall score range of 0 to 100 where higher scores represent better erection quality.	At 12 months post-surgery
Secondary	Hemoglobin Level at 2 Weeks After Surgery	Hemoglobin level at 2 weeks after surgery in grams per deciliter (g/dl).	2 weeks after surgery
Secondary	Number of Participants Requiring Transfusion During Hospitalization	Assess the number of participants requiring transfusion during hospitalization.	During hospital stay, up to 1 week

External Links

•   Preoperative recombinant human erythropoietin injection versus preoperative autologous blood donation in patients undergoing radical retropubic prostatectomy.
•   The preoperative use of erythropoietin stimulating proteins prior to radical prostatectomy is not associated with increased cardiovascular or thromboembolic morbidity or mortality.