Clinical trial NCT01466829: Treatment With PTH After Sternotomy in Cardiac Surgery Patients
Official title: Clinical Effects of Parathyroid Hormone as Adjuvant Therapy for Bone Healing After Sternotomy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Disruption or Dehiscence of Closure of Sternum or Sternotomy
Keywords: sternotomy
parathyroid hormone
bone healing
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Takeda
name: Aarhus University Hospital
First posted: 2011-11-08
Enrollment: 20
Sex: MALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aims of this study is to compare healing time and quality of newly formed bone in cardiac surgery patients treated with PTH post-surgically and a control group treated with saline.

Detailed description: Heart surgery is most commonly performed through a central division of the sternum, a sternotomy. This procedure provides full overview of the thoracic cavity and access to the organs within. At the department of Cardiothoracic \& Vascular Surgery at Skejby Hospital alone, over 1000 sternotomies are performed each year. When closing the sternum, the normal procedure is to use steel wires to hold the two sternal halves together. The patient receives no additional medical treatment to improve bone healing. Following surgery, sufficient healing of the sternum is important to prevent complications and to ensure a high level of life-quality for the patient. It has been shown that forces, equally to those produced during a normal cough, can displace the wire-fixated sternum by more than 2 mm. Reduced stability of the sternum has a negative impact on the healing process and increases the risk of infections. Another known complication to sternotomy is pseudoarthrosis (nonunion), which is caused by insufficient healing of the sternum and may result in instability, chronic pain and reduced quality of life. These complications result in prolonged admittance time, increased mortality and morbidity and from a financial point of view, increased treatment-costs for each patient.

Parathyroid hormone (PTH) is a well known anabolic drug and has been used to treat osteoporosis in post-menopausal women with great effect. A continuous high level of PTH decreases bone density and induces hypercalcemia, but if given once daily PTH has an anabolic effect on bone. It is being investigated if it is possible to use PTH in the treatment of other conditions, for example in the treatment of bone fractures.

Several studies, both clinical and experimental, show that PTH advances healing time and increases the quality of newly formed bone. It has also been shown to enable healing in sternal nonunion in one case-study. A recent human study of 102 osteoporotic women, with fractures of their radial bone, showed that daily injection with 20µg of the PTH-analog PTH1-34 (Teriparatide) reduces the fracture healing time. The effect of PTH on bone healing in sternum after a sternotomy has not previously been investigated.

In this study, we aim to investigate the effect of PTH on sternal healing in a clinical setup.

Eligibility criteria: Inclusion Criteria:

* Full sternotomy
* Not in chronic, systemic corticosteroid treatment.
* No Plavix treatment 5 days prior to surgery
* No known bone metabolic diseases.
* Replete vitamin D status (plasma 25-hydroxyvitamin D \>50 nmol/l)
* Normal serum levels of Calcium, Phosphate, inorganic, alkaline phosphatase (within reference interval).
* No known risk of osteosarcoma.
* Ability to understand and cooperate with the planned examinations.
* Ability to speak and understand Danish.

Exclusion Criteria:

* Re-operation
* Use of bone wax during surgery
* Prior radiation therapy involving the skeleton
* Severely impaired renal function.
* Known allergic reactions to any of the compounds in the trial medication.
* Current treatment with digoxin
* Major medical or social problems that will be likely to preclude participation
* Severely impaired lever function
* Unknown raised levels of bone specific alkaline phosphatase.

Primary outcomes:
measure: Computer Tomography
timeFrame: 6 weeks (± 1 week), 3 months (± 2 weeks) and 6 months (± 2 weeks)
Secondary outcomes:
measure: Questionnaires
timeFrame: Baseline, 6 weeks (± 1 week), 3 months (± 2 weeks), 6 months (± 2 weeks)
measure: Journal parameters
timeFrame: Baseline, 6 weeks (± 1 week), 3 months (± 2 weeks), 6 months (± 2 weeks)
Other outcomes:
Locations:
city: Aarhus N
country: Denmark
facility: Dept. of Cardiothoracic & Vascular Surgery, AArhus University Hospital, Skejby
Study officials:
affiliation: Dept. of Cardiothoracic & Vascular Surgery, Aarhus University Hospital, Skejby
name: Per Nielsen, MD
role: PRINCIPAL_INVESTIGATOR
References: