A Trial for Prevention of Recurrent Ischemic Priapism in Men With Sickle Cell Disease: A Pilot Study

NCT05142254 | Completed Phase 2 DMC

• 1 other identifier: 202504
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 2

Brief Summary

To conduct a randomized controlled internal pilot feasibility trial for the prevention of recurrent ischemic priapism referred to as the Priapism in Nigeria (PIN) trial. The study team will enroll a minimum of 30 participants and a maximum of 200 participants. Study investigators hypothesize that hydroxyurea therapy combined with tadalafil is superior to a combination of hydroxyurea and placebo in the prevention of recurrent ischemic priapism.

Conditions

Priapism Due to Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• A change in the recurrence rate of priapism

  We will use negative binomial regression to calculate the hazard rate for rate of priapism recurrence in both arms and determine whether there is a difference in recurrence between the two arms.

  Within a year, we will measure recurrence rates

Secondary Outcomes (10)

• The rate of vaso-occlusive pain, including hospitalizations

  Baseline- one year

• Change of erectile and sexual functions

  Baseline- one year

• Change of erectile and sexual functions

  Baseline- one year

• Change of erectile and sexual functions

  Baseline- one year

• Change of erectile and sexual functions

  Baseline- one year

Study Arms (2)

Tadalafil and Hydroxyurea

EXPERIMENTAL

Tadalafil 2.5-5 mg/day and Hydroxyurea 20 mg/kg/day

Drug: Tadalafil; Drug: Hydroxyurea

Placebo and Hydroxyurea

PLACEBO COMPARATOR

Placebo and Hydroxyurea 20 mg/kg/day

Drug: Hydroxyurea; Drug: Placebo

Interventions

Tadalafil DRUG

2.5-5 mg/day

Tadalafil and Hydroxyurea

Hydroxyurea DRUG

20 mg/kg/day

Placebo and Hydroxyurea; Tadalafil and Hydroxyurea

Placebo DRUG

identical placebo to tadalafil created by Bond Biochemical, who is manufacturing the tadalafil as well.

Placebo and Hydroxyurea

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Men with confirmed diagnosis of HbSS or Hb beta zero thalassemia
• Ages between 18 to 40 years
• Eligible study participants must receive care in an SCD clinic at AKTH and MMSH at the time of the recruitment
• Participants must commit to long-term follow-up and taking the trial medications
• At least 3 episodes of priapism, each lasting for no less than an hour in the past 6 months.
• Adequate renal and hepatic function (baseline liver enzymes and synthetic activities should be no more than four-fold above the reference ranges for Aminu Kano Teaching Hospital (AKTH). These are the ranges obtained in AKTH: Alkaline phosphatase: 42-110 U/L, Alanine transaminase: 4-34 U/L, Aspartate transaminase: 7-45 U/L, Albumin: 32-52 g/L, and Globulin: 32-43 g/L.

You may not qualify if:

• Individuals already enrolled in another clinical trial
• eGFR \<50ml/min
• Liver cirrhosis based on clinical history, laboratory data or both
• Previously known pulmonary hypertension based on TRJV greater than 3.0 m/sec
• Contraindications to tadalafil (arrhythmia, severe liver disease, concurrent use of nitrates, etc.) or hydroxyurea (leg ulcer, hypersensitivity, etc.).
• Patients who have penile prosthetic implants or shunts or any other surgical procedure on the penis
• Patients who have taken drugs/medications that may induce priapism over the 14 weeks before trial:
• Medications injected directly into the penis to treat erectile dysfunction, such as alprostadil, papaverine, phentolamine, and others
• Antidepressants, such as fluoxetine, bupropion, and sertraline
• Alpha blockers including prazosin, terazosin, doxazosin, and tamsulosin
• Medications used to treat anxiety or psychotic disorders, such as hydroxyzine, risperidone, olanzapine, lithium, clozapine, chlorpromazine, and thioridazine
• Blood thinners, such as warfarin and heparin
• Hormones such as testosterone or gonadotropin-releasing hormone
• Medications used to treat attention-deficit/hyperactivity disorder (ADHD), such as atomoxetine (Strattera)
• Alcohol, marijuana, cocaine and other illicit drug abuse can cause priapism

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (2)

Aminu Kano Teaching Hospital

Kano, Nigeria

Location

Murtala Mohammed Specialist Hospital

Kano, Nigeria

Location

Related Publications (15)

• Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN. Global burden of sickle cell anaemia in children under five, 2010-2050: modelling based on demographics, excess mortality, and interventions. PLoS Med. 2013;10(7):e1001484. doi: 10.1371/journal.pmed.1001484. Epub 2013 Jul 16.

  PMID: 23874164 BACKGROUND

• Anele UA, Morrison BF, Burnett AL. Molecular pathophysiology of priapism: emerging targets. Curr Drug Targets. 2015;16(5):474-83. doi: 10.2174/1389450115666141111111842.

  PMID: 25392014 BACKGROUND

• Huang AW, Muneyyirci-Delale O. Reproductive endocrine issues in men with sickle cell anemia. Andrology. 2017 Jul;5(4):679-690. doi: 10.1111/andr.12370. Epub 2017 Jun 29.

  PMID: 28662541 BACKGROUND

• Adeyoju AB, Olujohungbe AB, Morris J, Yardumian A, Bareford D, Akenova A, Akinyanju O, Cinkotai K, O'Reilly PH. Priapism in sickle-cell disease; incidence, risk factors and complications - an international multicentre study. BJU Int. 2002 Dec;90(9):898-902. doi: 10.1046/j.1464-410x.2002.03022.x.

  PMID: 12460353 BACKGROUND

• Emond AM, Holman R, Hayes RJ, Serjeant GR. Priapism and impotence in homozygous sickle cell disease. Arch Intern Med. 1980 Nov;140(11):1434-7.

  PMID: 6159833 BACKGROUND

• Serjeant G, Hambleton I. Priapism in Homozygous Sickle Cell Disease: A 40-year Study of the Natural History. West Indian Med J. 2015 Jun;64(3):175-80. doi: 10.7727/wimj.2014.119. Epub 2015 Apr 27.

  PMID: 26426165 BACKGROUND

• Virag R, Bachir D, Lee K, Galacteros F. Preventive treatment of priapism in sickle cell disease with oral and self-administered intracavernous injection of etilefrine. Urology. 1996 May;47(5):777-81; discussion 781. doi: 10.1016/s0090-4295(96)00027-1.

  PMID: 8650886 BACKGROUND

• Okpala I, Westerdale N, Jegede T, Cheung B. Etilefrine for the prevention of priapism in adult sickle cell disease. Br J Haematol. 2002 Sep;118(3):918-21. doi: 10.1046/j.1365-2141.2002.03691.x.

  PMID: 12181066 BACKGROUND

• Olujohungbe AB, Adeyoju A, Yardumian A, Akinyanju O, Morris J, Westerdale N, Akenova Y, Kehinde MO, Anie K, Howard J, Brooks A, Davis VA, Khoriatry AI. A prospective diary study of stuttering priapism in adolescents and young men with sickle cell anemia: report of an international randomized control trial--the priapism in sickle cell study. J Androl. 2011 Jul-Aug;32(4):375-82. doi: 10.2164/jandrol.110.010934. Epub 2010 Dec 2.

  PMID: 21127308 BACKGROUND

• Rachid-Filho D, Cavalcanti AG, Favorito LA, Costa WS, Sampaio FJ. Treatment of recurrent priapism in sickle cell anemia with finasteride: a new approach. Urology. 2009 Nov;74(5):1054-7. doi: 10.1016/j.urology.2009.04.071. Epub 2009 Jul 17.

  PMID: 19616292 BACKGROUND

• Abern MR, Levine LA. Ketoconazole and prednisone to prevent recurrent ischemic priapism. J Urol. 2009 Oct;182(4):1401-6. doi: 10.1016/j.juro.2009.06.040. Epub 2009 Aug 15.

  PMID: 19683289 BACKGROUND

• DeCastro BJ, Costabile RA, McMann LP, Peterson AC. Oral ketoconazole for prevention of postoperative penile erection: a placebo controlled, randomized, double-blind trial. J Urol. 2008 May;179(5):1930-2. doi: 10.1016/j.juro.2008.01.039. Epub 2008 Mar 18.

  PMID: 18353393 BACKGROUND

• Saad ST, Lajolo C, Gilli S, Marques Junior JF, Lima CS, Costa FF, Arruda VR. Follow-up of sickle cell disease patients with priapism treated by hydroxyurea. Am J Hematol. 2004 Sep;77(1):45-9. doi: 10.1002/ajh.20142.

  PMID: 15307105 BACKGROUND

• Burnett AL, Bivalacqua TJ, Champion HC, Musicki B. Feasibility of the use of phosphodiesterase type 5 inhibitors in a pharmacologic prevention program for recurrent priapism. J Sex Med. 2006 Nov;3(6):1077-1084. doi: 10.1111/j.1743-6109.2006.00333.x.

  PMID: 17100941 BACKGROUND

• Idris IM, Yusuf AA, Ismail II, Borodo AM, Hikima MS, Kana SA, Aliyu T, Musangedu K, Jibrilla AU, Aji SA, Kuliya-Gwarzo A, Mohammad K, Galadanci JA, Alkassim R, Suwaid MA, Hussaini N, Rodeghier M, Burnett AL, DeBaun MR. A controlled trial for preventing priapism in sickle cell anemia: hydroxyurea plus placebo vs hydroxyurea plus tadalafil. Blood. 2025 Jun 26;145(26):3101-3112. doi: 10.1182/blood.2024027898.

  PMID: 40073378 DERIVED

MeSH Terms

Interventions

Tadalafil; Hydroxyurea

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Urea; Amides; Organic Chemicals

Study Officials

• Leshana St. Jean, PhD

  Vanderbilt University Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The primary study statistician will be supported by a local statistician in Nigeria to perform the randomization process. After the random allocation, all study personnel and participants will be blinded to the treatment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D. MPH, Director Vanderbilt-Meharry Center for Excellence in Sickle Cell Disease

Model Details: Randomized Controlled Double-Blind Trial

Study Record Dates

• First Submitted: November 19, 2021
• First Posted: December 2, 2021
• Study Start: April 1, 2022
• Primary Completion: July 10, 2023
• Study Completion: November 9, 2023
• Last Updated: September 20, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

NG (2)