Effect of Postsurgical Systemic Doxycycline After Regenerative Periodontal Therapy

NCT01030666 | Terminated Phase 4 Results

• 1 other identifier: DoxP-01/2006
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 2

Brief Summary

Study Hypothesis: The administration of 200 mg doxycycline once a day for 7 days after regenerative periodontal therapy of infrabony defects improves the results of therapy (clinical vertical attachment gains \[CAL-V\], bony fill) and reduces postoperative flap dehiscence and defect exposure. In each of 90 patients one infrabony defect shall be treated by regenerative techniques (guided tissue regeneration \[GTR\], enamel matrix derivative \[EMD\]). Prior to , 6, 12, and 24 months after surgery clinical measurements (Plaque Index \[PlI\], probing depth \[PD\], vertical clinical attachment level \[CAL-V\], Gingival Index \[GI\]) and standardized radiographs are obtained.

Conditions

Periodontitis

Keywords

periodontal regeneration; radiographic bone fill; infrabony defects; randomized placebo-controlled clinical trial; guided tissue regeneration, periodontal

Outcome Measures

Primary Outcomes (1)

• Vertical Clinical Attachment (PAL-V) Gain 6 Months After Surgery

  Difference of PAL-V measurement at baseline and 6 months. PAL-V were measured to the nearest 0.5 mm using a straight manual periodontal probe (PCPUNC 15, Hu Friedy, Chicago, IL, USA). As reference for the PAL-V measurements, the cemento-enamel junction (CEJ) was used. If the CEJ is destroyed by a restoration (filling, crown) the margin of this restoration served as reference.

  Baseline to 6 months after surgery

Secondary Outcomes (1)

• Radiographic Bony Fill 12 Months After Surgery (Reduction of Distance Cemento-enamel Junction [CEJ] to Bony Defect [BD])

  Baseline to 12 months after surgery

Study Arms (2)

doxycycline

EXPERIMENTAL

The patients of the doxycycline group will take 200 mg doxycycline once a day for 7 days after regenerative therapy of an infrabony defects * modified/simplified papilla preservation flap; scaling * Prefgel/Emdogain * 0.12% chlorhexidine gluconate solution * Ibuprofen 400 mg (if necessary) * 1% chlorhexidine gluconate gel (if necessary)

Drug: Doxycycline; Procedure: modified/simplified papilla preservation flap; scaling; Biological: Prefgel/Emdogain; Drug: 0.12% chlorhexidine gluconate solution; Drug: Ibuprofen 400 mg (if necessary); Drug: 1% chlorhexidine gluconate gel (if necessary)

placebo

PLACEBO COMPARATOR

The patients of the control group will take placebo once a day for 7 days after regenerative therapy of an infrabony defect * modified/simplified papilla preservation flap; scaling * Prefgel/Emdogain * 0.12% chlorhexidine gluconate solution * Ibuprofen 400 mg (if necessary) * 1% chlorhexidine gluconate gel (if necessary)

Drug: Placebo; Procedure: modified/simplified papilla preservation flap; scaling; Biological: Prefgel/Emdogain; Drug: 0.12% chlorhexidine gluconate solution; Drug: Ibuprofen 400 mg (if necessary); Drug: 1% chlorhexidine gluconate gel (if necessary)

Interventions

Doxycycline DRUG

The patients of the doxycycline group will take 200 mg doxycycline once a day for 7 days after regenerative therapy of an infrabony defects.

Also known as: Doxy-Wolff 200

doxycycline

Placebo DRUG

The patients of the doxycycline group will take 200 mg placebo once a day for 7 days after regenerative therapy of an infrabony defects.

placebo

modified/simplified papilla preservation flap; scaling PROCEDURE

Following an intra-crevicular incision a mucoperiosteal flap was reflected to a height of 5 mm exposing the bony margin of the defect and allowing complete visualization of the infrabony lesion. The flap was designed according to the modified or simplified papilla preservation technique to obtain primary closure of the wound and the membrane respectively. The flap was extended at least one tooth mesially and distally of the defect side. After complete removal of inflammatory granulation tissue, the root surfaces were thoroughly scaled and root planed.

doxycycline; placebo

Prefgel/Emdogain BIOLOGICAL

When using EMD the root surfaces facing the infrabony defect were conditioned with EDTA (prefgel; Institut Straumann AG, Basel, Switzerland) for 2 min. first. Then the EDTA was washed out with plenty of saline. After drying the surfaces EMD was applied starting at the bottom of the defect and proceeding coronally.

Also known as: EDTA/Enamel matrix derivative (EMD)

doxycycline; placebo

0.12% chlorhexidine gluconate solution DRUG

Furthermore, all patients were advised to rinse with a 0.12% chlorhexidine gluconate solution (ParoEx; Butler, Kriftel, Germany) for 2 min. twice daily for 5-7 weeksafter surgery.

Also known as: ParoEx

doxycycline; placebo

Ibuprofen 400 mg (if necessary) DRUG

400 mg ibuprofen qd was prescribed for patient's comfort if necessary.

doxycycline; placebo

1% chlorhexidine gluconate gel (if necessary) DRUG

If soft tissue dehiscence was noted the patient was advised to use a 1% chlorhexidine gluconate gel (Chlorhexamed 1% Gel; GlaxoSmithKline, Bühl, Germany) twice daily

Also known as: Chlorhexamed 1% Gel

doxycycline; placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (at least 18 years of age) with moderate to severe periodontal disease (chronic and aggressive periodontitis) to be recruited from the Dept. of Periodontology, Centre for Dental, Oral, and Maxillofacial Medicine, Hospital of the Johann Wolfgang Goethe-University Frankfurt/Main and from the Section of Periodontology, Dept. of Conservative Dentistry, Clinic for Oral, Dental, and Maxillofacial Diseases, University Hospital Heidelberg
• completed initial periodontal treatment consisting of oral hygiene instruction, scaling and root planing under local anesthesia according the concept of full-mouth disinfection and re evaluation of the tissue response and the patient's plaque control 3 months later. Sites with infrabony defects and persisting pockets (PD \> 5 mm and bleeding on probing, BOP) that occur at re evaluation or supportive periodontal treatment (SPT) are subjected to surgical therapy.
• at least one radiographically detectable infrabony lesion
• good physical health and with effective individual plaque control (Full-mouth-plaque score PCR \</= 30% \[O'Leary et al. 1972\])
• interproximal angular defects on single-rooted teeth or multi-rooted teeth without furcation involvement, radiographic infrabony component \>/= 4 mm, vertical clinical attachment loss (CAL-V) \> 6 mm and PPD \>/= 6 mm
• Only women in childbearing age (\< 45 years) who provide contraception from screening to U2
• informed written consent

You may not qualify if:

• known allergies to tetracyclines or any components of the active drug or placebo
• severe liver dysfunction
• local or systemic antibiotic treatment during the last 3 months before surgery
• ineffective individual plaque control (PCR \> 30%)
• kidney dysfunction
• medication with barbiturate, carbamazepin, diphenyhydantoine, sulfonyl-urea, methoxyflurane, ciclosporin A, theophylline, isotretionin
• chronic alcohol abuse
• anticoagulative therapy
• need for antibiotic endocarditis prophylaxis
• pregnancy
• lactation

Sponsors & Collaborators

• Peter Eickholz: lead
• Heidelberg University: collaborator
• Dr. August Wolff GmbH & Co. KG Arzneimittel: collaborator
• Gaba International AG: collaborator

Study Sites (2)

Dept. of Periodontology, Center of Dental, Oral, and Maxillofacial Medicine, Johann Wolfgang Goethe-University

Frankfurt am Main, 60590, Germany

Location

Section of Periodontology, University Hospital Heidelberg

Heidelberg, 69120, Germany

Location

Related Publications (2)

• Rollke L, Schacher B, Wohlfeil M, Kim TS, Kaltschmitt J, Krieger J, Krigar DM, Reitmeir P, Eickholz P. Regenerative therapy of infrabony defects with or without systemic doxycycline. A randomized placebo-controlled trial. J Clin Periodontol. 2012 May;39(5):448-56. doi: 10.1111/j.1600-051X.2012.01861.x. Epub 2012 Mar 4.

  PMID: 22385260 RESULT

• Eickholz P, Rollke L, Schacher B, Wohlfeil M, Dannewitz B, Kaltschmitt J, Krieger JK, Krigar DM, Reitmeir P, Kim TS. Enamel matrix derivative in propylene glycol alginate for treatment of infrabony defects with or without systemic doxycycline: 12- and 24-month results. J Periodontol. 2014 May;85(5):669-75. doi: 10.1902/jop.2013.130290. Epub 2013 Sep 24.

  PMID: 24059744 RESULT

MeSH Terms

Conditions

Periodontitis

Interventions

Doxycycline; Tooth Exfoliation; enamel matrix proteins; Chlorhexidine; Ibuprofen; chlorhexidine gluconate; Gels

Condition Hierarchy (Ancestors)

Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Dental Physiological Phenomena; Digestive System and Oral Physiological Phenomena; Biguanides; Guanidines; Amidines; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Limitations and Caveats

The study had to be terminated due to shelf life of test drug running out prior to including 90 patients resulting in the low test power of 50%.

Results Point of Contact

• Title: Prof. Dr. Peter Eickholz
• Organization: JWGUniversity

eickholz@med.uni-frankfurt.de

+496963015642

Study Officials

• Peter Eickholz, Prof Dr

  Dept. of Periodontology, Center for Dental, Oral, and Maxillofacial Medicine, Johann Wolfgang Goethe-University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med. dent.

Study Record Dates

• First Submitted: December 10, 2009
• First Posted: December 11, 2009
• Study Start: April 1, 2007
• Primary Completion: January 1, 2011
• Study Completion: February 1, 2011
• Last Updated: November 3, 2016
• Results First Posted: November 27, 2012

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)