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

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

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.

Study Overview

• Status: Completed
• Conditions: Erectile Dysfunction; Prostate Cancer
• Intervention / Treatment: Drug: Erythropoietin (EPO); Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erythropoietin (EPO); 20,000 units of EPO given on the day before surgery, the day of surgery, and the day after surgery.	Drug: 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.
Placebo Comparator: Placebo; Placebo doses given the day before surgery, the day of surgery, and the day after surgery.	Drug: Placebo; Saline injection (solution prepared by research pharmacy) subcutaneously given the day before surgery, day of surgery, and the day after surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Hemoglobin Level at 2 Weeks After Surgery	Hemoglobin level at 2 weeks after surgery in grams per deciliter (g/dl).	2 weeks after surgery
Number of Participants Requiring Transfusion During Hospitalization	Assess the number of participants requiring transfusion during hospitalization.	During hospital stay, up to 1 week

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Mohamad E Allaf, MD, Johns Hopkins Hospital - Brady Urological Institute

Publications and helpful links

General Publications

• 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.
• 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. doi: 10.1097/01.ju.0000176808.94610.dd.
• 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. doi: 10.1111/j.1464-410X.2007.07194.x. Epub 2007 Sep 14.
• 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.
• 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 Jun;205(6):1681-1688. doi: 10.1097/JU.0000000000001586. Epub 2021 Feb 3.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: August 19, 2008
• First Submitted That Met QC Criteria: August 19, 2008
• First Posted (Estimate): August 20, 2008

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: March 15, 2021
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Erythropoietin; Erectile Dysfunction; Prostate Cancer; Radical Prostatectomy
• Additional Relevant MeSH Terms: Mental Disorders; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Prostatic Neoplasms; Erectile Dysfunction; Hematinics; Epoetin Alfa
• Other Study ID Numbers: IRB00048594; ERECT, EPO (Other Identifier: Johns Hopkins Brady Urological Institute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No