Aminophylline for Patients With Post-Dural Puncture Headache

Aminophylline for Patients With Post-Dural Puncture Headache: a Prospective, Multi-center, Randomized Controlled Trial

Post-dural puncture headache (PDPH) is the most common complication of lumbar puncture. Its clinical manifestations are pain in the forehead and the occipital region, or diffuse headache. The pain is dull or fluctuating, becoming worse when standing and better when lying down, and is often accompanied by symptoms including a stiff neck, tinnitus, hearing loss, photophobia, and nausea, which cause great suffering to the patients1. According to epidemiological data, approximately 10% to 30% of the patients who undergo lumbar puncture suffer from PDPH within 48 hours of the procedure.Currently, commonly used treatments for PDPH include rehydration, the administration of corticotropin, caffeine, or sumatriptan, and the application of an epidural blood patch. The efficacy of theophylline has been proven in a placebo-controlled study in which 17 PDPH patients received an intravenous (IV) injection of 200 mg theophylline. The Visual Analogic Scale scores 4 hours after treatment were significantly different compared with those of the placebo group5. At present, the clinical application of theophylline has been replaced by aminophylline and doxofylline, and it is difficult to purchase theophylline in most hospitals in China and other countries.

The Aminophylline for Patients With Post-Dural Puncture Headache trial, is a prospective,randomized,double-blind,placebo-controlled trial to evaluate the efficacy and safety of an IV injection of aminophylline on post-dural puncture headache.Eligible patients were randomized in a blinded fashion(1:1) to receive IV injection of aminophyllineor or sterile isotonic saline.The investigators estimate that this trial will demonstrate that an IV injection of aminophylline could be the preferred method for the clinical treatment of PDPH.

Study Overview

• Status: Completed
• Conditions: Post-dural Puncture Headache
• Intervention / Treatment: Drug: isotonic saline; Drug: Aminophylline

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Suzhou, Anhui, China
      • Suzhou Municipal Hospital
  • Hebei
    • Shijiazhuang, Hebei, China
      • the second hospital of Hebei medcial university
  • Henan
    • Zhengzhou, Henan, China
      • Henan Province Hospital of Traditional Chinese Medicine
  • Liaoning
    • Jinzhou, Liaoning, China
      • Jinzhou Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• headache has developed after the dural puncture;
• PDPH was defined according to the International Classification of Headache Disorders III (ICHD-3) criteria;
• The VAS score of the headache was 5 or more than 5;
• age between 18 and 70 years old.

Exclusion Criteria:

• a previous history of headache that could interfere with PDPH diagnosis;
• a history of central nervous system diseases including intracranial hemorrhage, seizures, intracranial hypertension, and hydrocephalus;
• a history of cardiovascular system diseases including coronary heart disease, arrhythmias, and hypertension;
• a history of peptic ulcer.
• women who were pregnant, nursing, or planning a pregnancy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aminophylline group; IV injection of aminophylline	Drug: Aminophylline
Placebo Comparator: isotonic saline group; IV injection of isotonic saline group	Drug: isotonic saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
pain on the Visual Analogue Scale	baseline phase
pain on the Visual Analogue Scale	0.5 hour after the Intervention
pain on the Visual Analogue Scale	1 hour after the Intervention
pain on the Visual Analogue Scale	8 hours after the Intervention
pain on the Visual Analogue Scale	1 day after the Intervention
pain on the Visual Analogue Scale	2 days after the Intervention

Secondary Outcome Measures

Outcome Measure	Time Frame
the overall response to treatment on the Patient Global Impression of Change	2 days after the Intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety (occurrence of adverse reactions)	The safety of the IV aminophylline treatment for PDPH was evaluated based on the occurrence of adverse reactions	Participants will be followed for the duration of hospital stay, an expected average of 7 days

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhengzhou University
• Investigators: Principal Investigator: Fang Xue, MD, the second hospital of Hebei medcial university; Principal Investigator: Dongsheng Guan, MD, Henan Province Hospital of Traditional Chinese Medicine; Principal Investigator: Changming Wan, MD, Jingzhou Central Hospital; Principal Investigator: Zhengfei Ma, MD, Suzhou Municipal Hospital

Publications and helpful links

General Publications

• Feuerstein TJ, Zeides A. Theophylline relieves headache following lumbar puncture. Placebo-controlled, double-blind pilot study. Klin Wochenschr. 1986 Mar 3;64(5):216-8. doi: 10.1007/BF01711650.
• Arroyo-Quiroz C, Kurth T, Cantu-Brito C, Lopez-Ridaura R, Romieu I, Lajous M. Lifetime prevalence and underdiagnosis of migraine in a population sample of Mexican women. Cephalalgia. 2014 Nov;34(13):1088-92. doi: 10.1177/0333102414529196. Epub 2014 Apr 7.
• Mills MD, Hogstrom KR, Fields RS. Determination of electron beam output factors for a 20-MeV linear accelerator. Med Phys. 1985 Jul-Aug;12(4):473-6. doi: 10.1118/1.595674.
• Hayallah AK, Talhouni AA, Alim AA. Design and synthesis of new 8-anilide theophylline derivatives as bronchodilators and antibacterial agents. Arch Pharm Res. 2012 Aug;35(8):1355-68. doi: 10.1007/s12272-012-0805-4. Epub 2012 Sep 1.
• Wu C, Guan D, Ren M, Ma Z, Wan C, Cui Y, Zhong P, Zhao W, Li C, Yan F, Xie J, Xue F, Lian Y, Liu H, Wang C, Ji X, Xie N. Aminophylline for treatment of postdural puncture headache: A randomized clinical trial. Neurology. 2018 Apr 24;90(17):e1523-e1529. doi: 10.1212/WNL.0000000000005351. Epub 2018 Mar 23.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: August 8, 2015
• First Submitted That Met QC Criteria: August 12, 2015
• First Posted (Estimate): August 13, 2015

Study Record Updates

• Last Update Posted (Estimate): October 31, 2016
• Last Update Submitted That Met QC Criteria: October 27, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Aminophylline; post-dural puncture headache
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders; Headache Disorders, Secondary; Wounds and Injuries; Headache; Post-Dural Puncture Headache; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Protective Agents; Cardiotonic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Aminophylline
• Other Study ID Numbers: FAHZZU-166